Thyroid Radioiodine Uptake Research Articles

Nonclassic TSH Resistance:TSHRMutation Carriers with Discrepantly High Thyroidal Iodine Uptake

Inactivating mutations in the TSH receptor gene (TSHR) cause TSH resistance. Most patients with TSH resistance have low to normal thyroidal radioiodine uptake (RAIU), which is consistent with the physiological knowledge that TSH stimulates iodine uptake. To date, only one TSHR mutation-carrying family with discrepantly high RAIU has been reported. We aimed to test whether TSHR mutation carriers with high RAIU are observed in a cohort of Japanese patients with congenital hypothyroidism (CH). Twenty-four Japanese CH patients with high RAIU were screened for TSHR mutations. The capacities of mutant TSHR to activate Gs- and Gq-coupled signaling pathways were evaluated in vitro. Two patients were found to have biallelic TSHR mutations: p.[T145I]+[R450H] in one and p.[R450H]+[I661fs] in the other. The two subjects had permanent CH with slightly high RAIU (41.8 and 43.0%, reference 8-40) but did not have goiter. One had a slightly high perchlorate discharge rate (10%, reference <10). Expression experiments revealed that T145I-TSHR retained partial ability to transduce both Gs- and Gq-coupled pathways, whereas I661fs-TSHR could transduce neither of them. R450H-TSHR had partial ability to transduce Gs-coupled signaling but had abrogated ability to transduce Gq-coupled signaling, indicating that coupling to Gq was dominantly affected. We show that 8% of Japanese CH patients with high RAIU (two in 24) has inactivating TSHR mutations. Expression of this apparently discrepant phenotype, which we term nonclassic TSH resistance, is presumably associated with the characteristic signaling property of the mutant TSHR, namely the Gq-dominant coupling defect.

A Study of the Etiology of Congenital Hypothyroidism in the Niigata Prefecture of Japan in Patients Born Between 1989 and 2005 and Evaluated at Ages 5–19

The prevalence of congenital hypothyroidism (CH) increased during the period 1994-2002 in Japan. The reasons for these recently described increases in the prevalence of CH remain unclear. Moreover, the proportion of patients with different etiologies CH in the more recently diagnosed patients has not been established. In this study, we determined the etiologies of CH that were detected by neonatal screening in Niigata refecture, Japan. A total of 100 patients having a diagnosis of CH (41 men and 59 women, aged 5-19 years old) were evaluated. To determine the etiology of CH, the patients underwent a ¹²³I thyroidal radioiodine uptake test, a scintigram, a saliva to plasma radioiodine ratio analysis, a perchlorate discharge test, thyroid ultrasonography, measurements of thyroidal function and thyroglobulin, and a thyrotropin (TSH)-releasing hormone tolerance test. Patients with overt CH (n=34, elevated TSH levels with low free thyroxine levels) made up 34% of the total group, 56% of the patients had subclinical CH (n=56, elevated TSH levels with normal free thyroxinelevels), and 10% had normal thyroid function. These were patients who were considered to have transient hypothyroidism or hyperthyrotropinemia. Thyroid dysgenesis was the diagnosis in 73% of patients with overt CH, and the most of these had ectopic thyroid tissue. In contrast, thyroid dysgenesis was the diagnosis in only 36% of the patients with subclinical CH. Only 50% of our patients with CH detected by neonatal screening had thyroid dysgenesis. With an increase in the percentage of patients with subclinical hypothyroidism, the prevalence of thyroid dyshormogenesis has increased. Studies of the frequency and etiology of CH should consider overt and subclinical CH separately.

Serum thyroxine and age — rather than thyroid volume and serum TSH — are determinants of the thyroid radioiodine uptake in patients with nodular goiter

Radioiodine (131I) therapy is widely used for treatment of non-toxic goiters. A limitation for this treatment is a low thyroid radioiodine uptake (RAIU), often encountered in these patients. To estimate the impact of various factors on the thyroid RAIU. We examined prospectively 170 patients (146 females; age range: 22-87 yrs) with nodular goiter (median 64 ml, range: 20-464 ml) selected for 131I therapy. Serum TSH was sub-normal in 42.4%. None were treated with anti-thyroid drugs. The thyroid RAIU was determined at 24h and 96 h. The goiter volume was measured by ultrasound (no.=127), or by magnetic resonance imaging (no.=43). The 24h and the 96 h RAIU were 34.2 ± 9.8(SD)% (range: 11.4-66.0%) and 34.0 ± 10.0% (range: 10.5-60.9%), respectively. Sixty-one patients had a 24h RAIU <30% and these individuals were older than patients with a 24h RAIU ≥ 30% (median 58 vs 51 yrs, p=0.02). These two subgroups did not differ significantly in other variables. Overall, the 24h RAIU was positively correlated to the serum (s) free T4-index (r=0.20, p=0.01), and negatively to age (r=-0.18, p=0.02), but not significantly related to serum TSH or thyroid volume. Age correlated positively with thyroid volume (r=0.31, p < 0.001). In a regression analysis, s-free T4-index and age remained as the only determinants of the 24h and the 96 h RAIU. In patients with a symptomatic nodular goiter, serum T4 and age are the major determinants of the thyroid RAIU. A sub-normal serum TSH is not a marker of a compromised thyroid RAIU but reflects that the iodine is confined to a few 'hot spots'.

Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification

The sodium-iodide symporter (NIS) mediates iodide uptake into the thyrocytes, which is important for the diagnosis and therapy of thyroid disorders. Decreased ability to uptake iodide in thyroid carcinomas reduces the efficacy of radioiodine therapy, and retinoic acid (RA) treatment reinduces iodide uptake. The effectiveness of treatment depends not only on iodide uptake but also on the ability of thyrocytes to organify iodine, which is catalyzed by thyroperoxidase (TPO) in the presence of H(2)O(2). Our goal was to determine the influence of RA on thyroid iodide uptake, iodine organification, and TPO and dual oxidase (DuOx) activities. Normal rats were treated with all-trans-RA or 13-cis-RA (100 or 1500 microg/100 g body weight (b.w.), s.c.) for 14 and 28 days. The 2 h thyroid radioiodine content significantly decreased in rats treated with all-trans-RA (100 microg/100 g b.w.) for 14 days. In this group, NIS function and TPO activity were unchanged, whereas DuOx activity was significantly decreased, which might have contributed to the decrease in iodine organification. Both doses of 13-cis-RA for 28 days increased the 15 min thyroid radioiodine uptake, while the 2 h radioiodide uptake increased only in rats treated with the highest dose of 13-cis-RA. While TPO activity did not change, H(2)O(2) generation was increased in this group, and serum thyroxine levels were normal. Since radioiodine half-life in the thyroid gland is important for treatment efficacy, our results highlight the importance of correctly choosing the RA isomer, the time and the dose of treatment, in order to improve the efficacy of radioiodine therapy.

Radioiodine treatment for non-toxic goitre.

There is no ideal treatment for benign multinodular goitre. Besides surgery, which is recommended for large goitres or when malignancy cannot be excluded, the non-surgical treatment options are levothyroxine therapy and radioiodine (131I) therapy. Conventional 131I therapy [without recombinant human thyroid-stimulating hormone (rhTSH)] has been used for more than a decade in symptomatic non-toxic multinodular goitre, and although it does lead to significant thyroid volume reduction, relatively high activities of radioiodine are needed because of a frequent finding of a low thyroid radioiodine uptake. rhTSH, even when used in very small doses in combination with 131I therapy, enhances the thyroid volume reduction at lower 131I activities by doubling the thyroid radioiodine uptake. However, before rhTSH stimulation can be routinely used by clinicians to optimise the 131I therapy in multinodular goitre, aspects of this association, such as the cost-benefit and optimum rhTSH dose and safety, will have to be sufficiently clarified.

Corrigendum to 'Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat' [ Journal of Feline Medicine and Surgery 10, 460-465

Department of Medical Imaging and Orthopedics of Small Animals, Faculty of Veterinary Science, University Ghent, Salisburylaan 133, 9820 Merelbeke, Belgium Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, University Ghent, Merelbeke, Belgium Department of Anatomy, Embryology, Histology and Medical Physics, Faculty of Medicine, University Ghent, Ghent, Belgium

Planning of 131I Therapy for Graves Disease Based on the Radiation Dose to Thyroid Follicular Cells: TABLE 1

We evaluated the effects on the absorbed dose to thyroid follicular cells of self-absorption of (131)I radiation (specifically, beta-rays) in the follicular colloid. Thyroid follicles were modeled as colloid-filled spheres, containing a uniform concentration of (131)I and surrounded by a concentric monolayer of cells. Assuming close packing of identical follicles, we used Monte Carlo simulation to assess the absorbed dose to follicular cells. Because of beta-ray self-absorption in colloidal spheres with radii larger than 50 mum, the absorbed dose to follicular cells is less than the average thyroid absorbed dose. For the same thyroid mass, radioiodine thyroid uptake, and effective half-life, patients with follicles with colloidal sphere radii of 100, 200, 300, and 400 microm should be administered 9%, 15%, 21%, and 30% more (131)I, respectively, than patients with colloidal sphere radii of less than 50 microm, to yield the same absorbed dose to follicular cells.

Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat.

Absorbed thyroid dose and effective half-life were determined in 46 hyperthyroid cats after treatment with a low dose (mean 111MBq) of radioiodine intravenously. Thirteen of these cats had received iohexol for glomerular filtration rate (GFR) measurement within 24h before treatment with radioiodine in view of another ongoing study at our institution. Pre-therapy values were obtained for total thyroxine (TT(4)) and for the thyroid to salivary gland ratio with sodium pertechnetate gamma-camera imaging. All cats underwent post-therapy scans at 24, 48 and 120 h for evaluation of radioactive iodine uptake (RAIU) and the effective half-life of radioiodine. The absorbed dose was calculated from the cumulative activity with Olinda software. Both groups were comparable in age, TT(4) and the ratio of thyroid activity to salivary gland activity. Statistical analysis revealed a significant decreased absorbed dose in the thyroid in the iohexol group. This decreased uptake was not accompanied by an decreased effective half-life of the radioiodine. The variation of inter-individual RAIU decreased in this group and more homogenous absorbed doses were obtained. No significant difference in outcome could be demonstrated. However, a tendency towards a higher number of residual hyperthyroidism in the iohexol group was noted (15 versus 6% in control group). This study demonstrates that iohexol interferes with the uptake of radioiodine in the hyperthyroid cat but does not provoke increased turnover. In this study, albeit including a small number of cats, outcome did not seem to be significantly affected.

The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is caused by excessive hormone synthesis and release (AIT I) or a destructive process (AIT II). This differentiation has important therapeutic implications. To evaluate (99m)Tc-sestaMIBI (MIBI) thyroid scintigraphy in addition to other diagnostic tools in the diagnosis and management of AIT. Thyroid and (99m)Tc-MIBI scintigraphies were performed in 20 consecutive AIT patients, along with a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid colour-flow Doppler sonography (CFDS) and thyroid radioiodine uptake (RAIU)). On the basis of instrumental and laboratory data (excluding thyroid (99m)Tc-MIBI scintigraphy) and follow-up, AIT patients could be subdivided into six with AIT I, ten with AIT II and four with indefinite forms of AIT (AIT Ind). (99m)Tc-MIBI uptake results were normal/increased in all the six patients with AIT I and absent in all the ten patients with AIT II. The remaining four patients with AIT Ind showed low, patchy and persistent uptake in two cases and in the other two evident MIBI uptake followed by a rapid washout. MIBI scintigraphy was superior to all other diagnostic tools, including CFDS (suggestive of AIT I in three patients with AIT II and of AIT II in three with AIT Ind) and RAIU, which was measurable in all patients with AIT I, and also in four out of the ten with AIT II. Thyroid MIBI scintigraphy may be proposed as an easy and highly effective tool for the differential diagnosis of different forms of AIT.

Thyroid Function and Body Weight Programming by Neonatal Hyperthyroidism in Rats - The Role of Leptin and Deiodinase Activities

Several authors have shown that secondary hypothyroidism was programed by neonatal thyroxine (T4) treatment. However, the associated changes of body weight (BW) were less studied, especially those related to the body fat proportion. Here, we have evaluated the effect of neonatal thyroxine treatment on BW, fat proportion, serum leptin, and thyroid function of 60-day-old rats. Wistar rats were treated with thyroxine (50 microg/100 g BW, ip) (T) or saline (S), during the first 10 days of life. BW, nose-rump length (NRL), and food consumption were monitored for 60 days, when the animals were sacrificed. Thyroid function was evaluated by thyroid radioiodine uptake (RAIU), serum T3, T4, TSH, and liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD) and type 1 and 2 deiodinases (D1 and D2) activities, which are thyroid hormone-dependent enzymes. T animals showed lower food intake, BW and NRL, but higher total fat mass (+33%) and serum leptin (+46%). They also showed lower serum T3 (-23%), T4 (-32%), TSH (-36%), RAIU (-29%) and mGPD activity (-22%). Hypothalamic and pituitary D2 activities were higher (+24% and 1.4 fold, respectively), while brown adipose tissue (BAT) D2 and skeletal muscle D1 activities were lower (-30% and -62%, respectively). Thus, neonatal hyperthyroidism programs for a higher fat proportion and hyperleptinemia, which can explain the lower food intake. The TH-dependent enzymes activities changed accordingly, except for the decrease in BAT D2, which may be due the role played by the hyperleptinemia. Finally, the decrease in peripheral deiodination may contribute to a lower me-tabolic rate that may increase the adiposity.

Could improved ultrasound and power Doppler replace thyroidal radioiodine uptake to assess thyroid disease?

Could improved ultrasound and power Doppler replace thyroidal radioiodine uptake to assess thyroid disease?

Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) may be caused by excessive thyroidal hormone synthesis and release (type 1) or by a destructive process (type 2). This differentiation is considered essential for therapeutic choice. To evaluate the utility of color-flow Doppler sonography (CFDS) in the differential diagnosis and management of AIT. The clinical and laboratory data, thyroid sonography (grayscale sonography [GSS], CFDS), thyroid radioiodine uptake (RAIU) and thyroid scintigraphy, treatment, and clinical outcome were retrospectively reviewed in 21 AIT patients. The CFDS pattern of thyroid nodules was separately described from that of the perinodular parenchyma, and AIT was classified as type 1 (increased blood flow) or type 2 (low/no blood flow). Type 1 AIT patients were treated with methimazole (alone or associated with potassium perchlorate), while type 2 patients were treated with prednisone or amiodarone withdrawal alone. Eleven patients with increased blood flow were considered as type 1, and 10 with low/no blood flow as type 2. Ten of the 11 patients in the first group showed a hypervascular nodular pattern, while one showed a hypervascular parenchymal pattern. Clinical diagnoses were toxic nodular goiter and Graves' disease, respectively. Of the 10 patients with low/no blood flow, six had normal thyroid volume, three small diffuse goiter, and one small multinodular goiter. The clinical outcome showed that 20 of the 21 patients were treatment responsive. CFDS is a useful tool in the differential diagnosis of AIT. This differentiation appeared to be of clinical relevance as regards therapeutic choice. Separate evaluation of parenchymal blood flow from that of nodules may prove beneficial in the diagnosis of underlying thyroid diseases in patients with type 1 AIT.

Amiodarone Inhibits Thyroidal Iodide Transportin Vitroby a Cyclic Adenosine 5′-Monophosphate- and Iodine-Independent Mechanism

Thyroid side effects are common in patients treated for cardiac arrhythmias with amiodarone (AM). A major disturbance is inhibited thyroidal radioiodine uptake in AM-induced thyrotoxicosis, which makes 131I therapy ineffective. On the other hand, failure to escape from the Wolff-Chaikoff effect by down-regulation of the sodium/iodide symporter (NIS) is proposed to explain AM-induced hypothyroidism. However, previously no experimental studies on the possible mechanisms have been conducted. We therefore investigated the early effects of AM on thyroidal iodide transport using bicameral chamber cultures of primary pig thyrocytes that reproduce the three tissue compartments (epithelium, lumen, and extrafollicular space) of the gland. AM dose-dependently (1-50 microm) inhibited the TSH-stimulated transepithelial (basal to apical) transport of 125I- by up to 90%. The inhibitory effect was noticed already after 8 h and was further pronounced after 1-4 d, depending on the AM concentration. The intracellularly accumulated 125I- was reduced by perchlorate but not AM, and quantitative real-time RT-PCR revealed no change in the NIS expression in AM-treated cells. Blocking of cAMP degradation with 3-isobutyl-1-methylxanthine or withdrawal of AM reversed AM-induced changes in electrolyte transport but were unable to recover the suppressed 125I- transport. The iodine-free AM analog dronedarone also inhibited 125I- transport to the same extent as AM. The findings indicate that AM blocks thyroidal iodide uptake by reducing the iodide permeability of the apical plasma membrane of the thyroid epithelial cells. The effect is iodine independent and long-lasting and does not involve impaired function of NIS or the TSH receptor/cAMP signaling pathway.

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

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. This was a short-term, observational study. 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. 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. 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.

The NAS Perchlorate Review: Second-Guessing the Experts

The Committee to Assess the Health Implications of Perchlorate Ingestion [National Academy of Sciences (NAS)] released its final report [National Research Council (NRC) 2005] in January 2005, recommending a reference dose (RfD) for perchlorate of 0.0007 mg/kg-day. In a commentary published online on 25 May 2005, Ginsberg and Rice (2005) criticized the adequacy of the NAS committee’s scientific deliberations, mischaracterizing the studies reviewed by the committee and second-guessing its conclusions. Ginsberg and Rice (2005) implied that the U.S. Environmental Protections Agency’s (EPA’s) previous draft RfD of 0.00003 mg/kg-day (U. S. EPA 2002)—and by inference the Massachusetts perchlorate risk assessment [Massachusetts Department of Environmental Protection (Mass DEP) 2004] that mirrored the U.S. EPA’s approach and which Ginsberg and Rice peer reviewed—is more scientifically defensible. The NAS committee was composed of 15 leading physicians and scientists with combined range of expertise to evaluate every scientific aspect of the perchlorate database and of the U.S. EPA’s assessment of that database. The makeup of this committee and its credentials are available on the NAS website (NAS 2004). The NAS committee studied and deliberated for more than 15 months before issuing its report. Those deliberations included three public meetings during which it accepted verbal and/or written comments from the U.S. EPA, other government agencies, industry, states, environmental groups, and attorneys. After careful study and consideration of the scientific studies that formed the basis for the U.S. EPA’s 2002 draft RfD as well as the 2004 Massachusetts risk assessment (Mass DEP 2004), the NAS committee considered several of the animal studies … to be flawed in their design and execution. Conclusions based on those studies, particularly the neurodevelopmental studies, were not supported by the results of the studies. Although Ginsberg and Rice (2005) implied that the NAS committee should have considered the threshold for measurable iodine uptake inhibition “adverse” and that the NAS inadvertently left out the “A” in NOAEL (no observed adverse effect level), the committee decisively stated that “inhibition of iodide uptake by the thyroid clearly is not an adverse effect.” The committee carefully considered the issue of a NOEL (no observed effect level) and a NOAEL. Based on a clinical study of patients receiving perchlorate long term, the NAS established the NOAEL as 0.4 mg/kg-day (57 times higher than its identified NOEL). Ginsberg and Rice (2005) further expressed concerns regarding perchlorate in breast milk and the subsequent possibility of decreased breast milk iodine, citing Kirk et al. (2005) and Gibbs (2004). Kirk et al. (2005) reported perchlorate and iodide levels in breast milk samples and noted that “if we take all the available data, there is no meaningful correlation between the perchlorate and iodide levels in breast milk.” The study from Chile that Ginsberg and Rice refer to as Gibbs (2004) is now published as Tellez et al. (2005). The study found that iodine nutrition of pregnant women in Chile is very similar to that in the United States. Tellez et al. (2005) found no maternal or neonatal perchlorate-related thyroid effects or decreases in breast milk iodine with perchlorate doses spanning the 0.0007–0.007 mg/kg-day range. Ginsberg and Rice (2005) argued that perchlorate database deficiencies require an additional uncertainty factor of 3–10 because of key data gaps, citing breast milk concerns and the extrapolation from a 14-day exposure study to chronic exposure. The NAS committee (NRC 2005) considered this and concluded that if inhibition of iodide uptake by the thyroid is duration-dependent, the effect should decrease rather than increase with time, because compensation would increase the activity of the sodium-iodide symporter and therefore increase iodide transport into the thyroid. Evidence has subsequently shown this to be the case (Braverman et al. 2005). The California EPA perchlorate risk assessment (California EPA 2004) relied on the same studies as the NRC report (NRC 2005). The “point of departure” was based on iodine uptake inhibition by Greer et al. (2002), and a total uncertainty factor of 10 was applied to account for interindividual variability. After reviewing the NRC report (NRC 2005), the California EPA elected not to change its risk assessment or public health goal (California EPA 2005). In summary, the concerns presented by Ginsberg and Rice (2005) have already been addressed thoroughly by experts on perchlorate and thyroid toxicology and were found to be unsubstantiated. The NAS committee and other experts came to this conclusion based on a comprehensive review of the science in the field, not based entirely on an individual study, which has been mischaracterized by Ginsberg and Rice.

The effects of taking chronic nitrate by drinking water on thyroid functions and morphology

Nitrate incorporation in humans takes place via drinking water and food. The water used for drinking and cooking in the goitrous areas is high in nitrate content. The aim of the present study was to evaluate both chronic effects and the dose-response relationship of nitrate on thyroid functions. A total of rats were divided into 5 work groups and sodium nitrate was added to their drinking water in different concentrations (0, 50, 100, 250 and 500 mg/l) over a 30-week period. The radioiodine uptake of thyroid was decreased in the 50 mg/l nitrate group, whereas it was increased in the 250 and 500 mg/l nitrate groups as compared to control. All hormones of thyroid gland except total thyroxine and thyroid-stimulating hormone were decreased in the 50, 250 and 500 mg/l nitrate groups. However, the level of total thyroxin was increased in the 100 mg/l nitrate group. Thyroid gland weights were increased in all experimental groups. Histomorphological changes were observed in the 250 and 500 mg/l nitrate groups. These findings suggest that nitrate impairs thyroid function involving the hypothalamo-hypophysio-thyroid axis. This observation could contribute to the current discussion about the acceptable daily intake of nitrate, as well as drinking water nitrate standard safety margins.

CALCIUM IODATE???ANOTHER EFFECTIVE BLOCKER OF RADIOIODINE UPTAKE BY THE THYROID GLAND

KI and KIO3 are the commonly used prophylactic drugs for the protection of thyroid glands against radioiodine. In this study, we have demonstrated the use of another iodine containing salt, calcium iodate [Ca(IO3)2], as an effective blocker of radioiodine uptake by the thyroid gland in rats. Ca(IO3)2 is permitted by the FDA as a food additive and is "generally regarded as safe" (GRAS, CFR No.1206). We have also compared the efficacy of Ca(IO3)2 with KIO3 in blocking thyroidal uptake of radioiodine, which could be important considering the better shelf life of Ca(IO3)2. Laboratory rats were administered 131I and stable iodide in the form of KIO3 or Ca(IO3)2 was given orally, 2 h after the administration of 131I. All the animals were monitored for whole body retention (WBR) of 131I, at 24 h and further for 14 d. The results of the present study provide us with evidence that Ca(IO3)2 can serve as another promising radioiodine blocker, and is as equipotent as KI/KIO3 in protecting the thyroid gland. We have not found any studies that examined the property of Ca(IO3)2 in blocking radioiodine uptake by the thyroid gland and the present study is an attempt in this direction.

Anaplastic Thyroid Carcinoma With Thyrotoxicosis and Hypoparathyroidism

To describe a patient who presented with anaplastic thyroid carcinoma and thyrotoxicosis in whom hypoparathyroidism developed. We present the clinical and laboratory findings in a patient with anaplastic thyroid carcinoma and thyrotoxicosis. We also review the literature for previous cases of anaplastic thyroid carcinoma with thyrotoxicosis. A 74-year-old man presented with left-sided neck pain and a rapidly enlarging neck mass. Initial thyroid function tests revealed the following: thyrotropin (thyroid-stimulating hormone or TSH) 0.03 microIU/mL, free thyroxine 1.28 ng/dL, and total triiodothyronine 119 ng/dL. A thyroid radioiodine uptake scan was 2.2% at 25 hours. Pathology examination of the neck mass disclosed anaplastic thyroid carcinoma. His thyrotoxicosis was managed with beta-adrenergic blockade. The thyroid carcinoma was treated palliatively with external beam irradiation. During week 9 after the patient's initial presentation, symptomatic hypocalcemia developed, with an ionized serum calcium level of 0.75 mmol/L (normal range, 1.15 to 1.29) and a parathyroid hormone level of 21.2 pg/mL (normal range, 10 to 65). He was given calcium gluconate intravenously for initial management, followed by orally administered calcium carbonate and calcitriol. At week 15, he died of complications attributable to anaplastic thyroid carcinoma. Thyrotoxicosis due to thyroiditis is a rare initial manifestation of anaplastic thyroid carcinoma. Hypoparathyroidism due to anaplastic thyroid carcinoma has not been reported previously.

Perchlorate and Thyroid Function: What are the Environmental Issues?

Ammonium perchlorate, used in the solid-propellant of rocket engines, has contaminated some water supplies and represents a potential public health hazard. Its toxicity is the result of the inhibition of the sodium iodide symporter resulting in reduced iodide uptake, possibly leading to reduced production of thyroid hormone. The fetus is the most vulnerable subject. Studies of newborn screening for thyroid function have yielded conflicting results and have not measured perchlorate or iodine intake. Based on short-term clinical studies in adults, less than 0.5 mg perchlorate per 70-kg adult will not lower thyroid uptake of radioiodine, while 1.6 mg/kg per day will lower thyroid uptake by 20%. To avoid interference with thyroid function, the California Office of Environmental Health Hazard Assessment recommended a public health goal of 6 microg perchlorate per liter of drinking water, but approximately three times that concentration is likely to be safe.

Population Biokinetic Modeling of Thyroid Uptake and Retention of Radioiodine

The aim of this study was to build a population biokinetic model for the uptake and retention of radioiodine in the thyroid of hyperthyroid patients. At Malmö University Hospital (Malmö, Sweden), a database with detailed information from (131)I-iodide therapies has been created. The database consisted of uptake measurement from 422 patients with the diagnoses of diffuse goiter, multinodular goiter, adenoma, and undefined. In total, 2013 uptake measurements, performed from 3 hours to 9 days after intake of a test activity of (131)I, were included. Nonlinear mixed effect modeling (NLME) was used to model the population biokinetics of (131)I. The structural model was parameterized in terms of the level of uptake (A), the rate constant for the absorption to the thyroid (k(a)) and the rate constant for the output from the thyroid (k(e)). Interindividual and interoccasion variabilities were added to all three structural parameters. The following covariates were found to significantly affect the structural model parameters: Diagnosis on A, k(a) and K(e), volume of the thyroid on A and k(a), and age on k(a) and k(e). The interindividual and interoccasion variabilities were in the range of 8%-28%. The variance of the residual error, modeled as an additive, was low. This type of modeling is a powerful tool for biokinetic studies and should be used in other biokinetic areas of radioiodine therapy, such as radiation dosimetry.