Low Iodine Diet Research Articles

Dietary evaluation of a low-iodine diet in Korean thyroid cancer patients preparing for radioactive iodine therapy in an iodine-rich region.

BACKGROUND/OBJECTIVESDespite the importance of a low-iodine diet (LID) for thyroid cancer patients preparing for radioactive iodine (RAI) therapy, few studies have evaluated dietary intake during LID. This study evaluated the amount of dietary iodine intake and its major food sources during a typical diet and during LID periods for thyroid cancer patients preparing for RAI therapy, and examined how the type of nutrition education of LID affects iodine intake.SUBJECTS/METHODSA total of 92 differentiated thyroid cancer patients with total thyroidectomy were enrolled from Seoul National University Hospital. All subjects completed three days of dietary records during usual and low-iodine diets before 131I administration.RESULTSThe median iodine intake was 290 µg/day on the usual diet and 63.2 µg/day on the LID. The major food groups during the usual diet were seaweed, salted vegetables, fish, milk, and dairy products and the consumption of these foods decreased significantly during LID. The mean energy intake on the LID was 1,325 kcal, which was 446 kcal lower than on the usual diet (1,771 kcal). By avoiding iodine, the intake of most other nutrients, including sodium, was significantly reduced during LID (P < 0.005). Regarding nutritional education, intensive education was more effective than a simple education at reducing iodine intake.CONCLUSIONIodine intake for thyroid cancer patients was significantly reduced during LID and was within the recommended amount. However, the intake of most other nutrients and calories was also reduced. Future studies are needed to develop a practical dietary protocol for a LID in Korean patients.

Low iodine diet does not improve the efficacy of radioiodine for the treatment of Graves’ disease

Consuming a low-iodine diet (LID) is a widely accepted practice before administering radioiodine (131I) to evaluate and to treat thyroid disease. Although this procedure is well established for the management of patients with differentiated thyroid cancer, its use in patients with benign disease is unclear. So, we aimed to evaluate the influence of a LID on the outcome in patients with Graves' disease (GD) treated with 131I. We evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31) consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to maintain a regular diet (RD). The LID group experienced a 23% decrease in urinary iodine after 1 week on the diet and a significant 42% decrease after 2 weeks on the diet. The majority (53%) of the patients in the LID group had urinary iodine levels that were consistent with deficient iodine intake. However, there was no difference in the rate of hyperthyroidism's cure between the LID and the RD groups 6 months after 131I therapy. Furthermore, the therapeutic efficacy did not differ in patients with varying degrees of sufficient iodine intake (corresponding urinary iodine levels: < 10 μg/dL is deficient; 10-29.9 μg/dL is sufficient; and > 30 μg/dL is excessive). In the present study, we demonstrated that although a LID decreased urinary iodine levels, those levels corresponding with sufficient or a mild excess in iodine intake did not compromise the therapeutic efficacy of 131I for the treatment of GD.

Association between iodine intake and treatment outcomes of radioiodine remnant ablation in patients with papillary thyroid cancer

Objective To evaluate the association between iodine intake and treatment outcomes of radioiodine remnant ablation in patients with papillary thyroid cancer (PTC), and to investigate the determinants related to the ablation efficacy. Methods A total of 95 PTC patients (28 males, 67 females; average age 39.8 years) without distant metastases from January 2013 to May 2014 were enrolled in this retrospective study. All patients underwent total thyroidectomy and 2-4 weeks of low iodine diet (LID) before initial 131I therapy. Patients were divided into 3 groups according to urinary iodine excretion (UIE): moderate-severe iodine deficiency group (0<UIE<50 μg/L, n=30), mild iodine deficiency group (50 μg/L≤UIE<100 μg/L, n=26), adequate iodine group (100 μg/L≤UIE<300 μg/L, n=39). Patients were followed up for 3-6 months after radioiodine ablation, successful ablation was defined as no visible uptake in the thyroid bed on diagnostic 131I whole body scan and Tg level <2 μg/L (with negative TgAb), or no visible uptake in thyroid bed on posttreatment 131I whole body scan. χ2 test, two-sample t test, Mann-Whitney u test and logistic regression analysis were performed. Results In all, 84.2%(80/95)of patients were successfully ablated. The successful rates in the three iodine intake groups were 96.7%(29/30), 84.6%(22/26) and 74.4%(29/39), respectively, with significant difference (χ2=7.374, P<0.05). Univariate analysis revealed that UIE, pre-treatment TSH, pre-treatment Tg and the amount of remnant thyroid tissue at ablation affected ablation efficacy (χ2=7.374, t=2.037, z=-2.966, χ2=4.144, all P<0.05). Logistic regression showed that the level of pre-treatment Tg (P<0.05) and iodine intake (P<0.05) were independent factors of ablation efficacy. Conclusion Iodine intake before 131I remnant ablation is one of the important factors affecting treatment outcomes. Thyroid remnant could be more successfully ablated if reasonable LID protocols be adopted according to the iodine nutritional status before treatment. Key words: Thyroid neoplasms; Surgery, operative; Radiotherapy; Iodine radioisotopes

Low iodine diet in differentiated thyroid cancer: a review.

Radioactive iodine (RAI) ablation is a beneficial, adjuvant therapy for the management of differentiated thyroid cancer (DTC) after thyroidectomy. The goal of RAI is to destroy remnant thyroid and microscopic cancerous tissue. Radioactive iodine uptake is enhanced by elevating TSH levels and initiating a low iodine diet (LID) prior to ablation. An ideal LID should preferably not exceed 50 mcg/day of dietary iodine for 1-2 weeks, although the duration may be shortened to a week with a structured patient education programme. A pre-ablation spot urinary iodine concentration (UIC) of <100 mcg/l and/or a urinary iodine to creatinine ratio (UICR) of <100 mcg/gCr would support an adequate LID preparation. Hyponatraemia, most likely due to iatrogenic hypothyroidism, is a potential side effect associated with LID and occurs during and a few days after the LID. Although the overall incidence of hyponatraemia is low, patients at high risk (older age, female sex, use of thiazide diuretics) may benefit from serum sodium monitoring. The existing evidence on the impact of LID on RAI ablation has been largely inconsistent due to retrospective study designs and the lack of an objective measurement of urinary iodine levels. Future large prospective randomized control trials are needed to elucidate and confirm the crucial role of LID in achieving successful RAI ablation and greater disease-free survival in DTC.

The immediate and late effects of thyroid hormone (triiodothyronine) on murine coagulation gene transcription.

Thyroid dysfunction is associated with changes in coagulation. The aim of our study was to gain more insight into the role of thyroid hormone in coagulation control. C57Black/6J mice received a low-iodine diet and drinking water supplemented with perchlorate to suppress endogenous triiodothyronine (T3) and thyroxine (T4) production. Under these conditions, the impact of exogenous T3 on plasma coagulation, and hepatic and vessel-wall-associated coagulation gene transcription was studied in a short- (4 hours) and long-term (14 days) setting. Comparing euthyroid conditions (normal mice), with hypothyroidism (conditions of a shortage of thyroid hormone) and those with replacement by incremental doses of T3, dosages of 0 and 0.5 μg T3/mouse/day were selected to study the impact of T3 on coagulation gene transcription. Under these conditions, a single injection of T3 injection increased strongly hepatic transcript levels of the well-characterized T3-responsive genes deiodinase type 1 (Dio1) and Spot14 within 4 hours. This coincided with significantly reduced mRNA levels of Fgg, Serpinc1, Proc, Proz, and Serpin10, and the reduction of the latter three persisted upon daily treatment with T3 for 14 days. Prolonged T3 treatment induced a significant down-regulation in factor (F) 2, F9 and F10 transcript levels, while F11 and F12 levels increased. Activity levels in plasma largely paralleled these mRNA changes. Thbd transcript levels in the lung (vessel-wall-associated coagulation) were significantly up-regulated after a single T3 injection, and persisted upon prolonged T3 exposure. Two-week T3 administration also resulted in increased Vwf and Tfpi mRNA levels, whereas Tf levels decreased. These data showed that T3 has specific effects on coagulation, with Fgg, Serpinc1, Proc, Proz, Serpin10 and Thbd responding rapidly, making these likely direct thyroid hormone receptor targets. F2, F9, F10, F11, F12, Vwf, Tf and Tfpi are late responding genes and probably indirectly modulated by T3.

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Due to the high variance in available protocols on iodide-131 (¹³¹I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of ¹³¹I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T₄ concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and ^99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) ¹³¹I alone was not sufficient to abolish thyroidal T₄ production, 500 µCi (18.5 MBq) ¹³¹I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high ¹³¹I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) ¹³¹I decreased serum T₄ concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. ^99mTc-pertechnetate scintigraphy revealed absence of thyroidal ^99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Pingxiao capsule combined Longxuejie capsule in the treatment of nodular goiter

Objective To assess the clinical efficacy of Pingxiao capsule combined Longxuejie capsule in the treatment of nodular goiter. Methods A total of 100 patients with nodular goiter from Jiangsu Provincial Hospital of Chinese Medicine were randomized into a treatment group and a control group, with 50 patients in each group. In addition to low iodine diet, the treatment group was treated with Pingxiao capsule (1.15 g, thrice daily) plus Longxuejie capsule (1.2 g, thrice daily), while the control group was treated with levothyroxine sodium tablets (5 g, once daily), both for 3 months. The max diameter of thyroid nodule and the thyroid function were detected before and after the treatment. Results One patient in the treatment group and 3 patients in the control group were lost to follow-up. The max diameter of thyroid nodule were significantly decreased compared with before the treatment in the treatment group (1.49 ± 0.69 cm vs. 2.14 ± 0.87 cm; t=4.113, P=0.000) and not in the control group (1.94 ± 1.15 cm vs. 2.21 ± 1.03 cm; t=1.220, P=0.226). The free thyroxine levels were significantly increased compared with before the treatment both in the treatment group (0.83 ± 0.11 ng/dl vs. 0.77 ± 0.15 ng/dl; t=2.266, P=0.026) and in the control group (0.78 ± 0.16 ng/dl vs. 0.64 ± 0.23 ng/dl; t=3.459, P=0.001), and greater in the control group (P<0.01). The thyroid stimulating hormone level was significantly decreased compared with before the treatment in the in the control group (1.44 ± 1.59 U/ml vs. 2.28 ± 0.92 U/ml; t=3.208, P=0.002) and not in treatment group (1.98 ± 1.09 U/ml vs. 2.31 ± 0.87 U/ml; t=1.667, P=0.099). There were significant difference in free triiodothyronine levels between before and after the treatment both in the treatment group (3.31 ± 0.29 pg/ml vs. 3.27 ± 0.31 pg/ml; t=0.663, P=0.509) and in the control group (3.39 ± 0.13 pg/ml vs. 3.44 ± 0.16 pg/ml; t=1.694, P=0.094). The total effective rate in the treatment group was significantly higher than that in the control group (83.7% vs. 63.8%; χ2=3.929, P=0.048). Conclusion Pingxiao capsule combined Longxuejie capsule can reduce the size of thyroid nodules in patients with nodular goiter. Key words: Goiter, Nodular; Pingxiao capsule; Longxuejie capsules

Effect of a Low Iodine Diet vs. Restricted Iodine Diet on Postsurgical Preparation for Radioiodine Ablation Therapy in Thyroid Carcinoma Patients

PurposeThe radioiodine ablation therapy is required for patients who underwent a total thyroidectomy. Through a comparative review of a low iodine diet (LID) and a restricted iodine diet (RID), the study aims to suggest guidelines that are suitable for the conditions of Korea.Materials and MethodsThe study was conducted with 101 patients. With 24-hour urine samples from the patients after a 2-week restricted diet and after a 4-week restricted diet, the amount of iodine in the urine was estimated. The consumed radioiodine amounts for 2 hours and 24 hours were calculated.ResultsThis study was conducted with 47 LID patients and 54 RID patients. The amounts of iodine in urine, the 2-week case and 4-week case for each group showed no significant differences. The amounts of iodine in urine between the two groups were both included in the range of the criteria for radioiodine ablation therapy. Also, 2 hours and 24 hours radioiodine consumption measured after 4-week restrictive diet did not show statistical differences between two groups.ConclusionA 2-week RID can be considered as a type of radioiodine ablation therapy after patients undergo a total thyroidectomy.

Effect of Short Term Thyroxin Withdrawal on Health Related Quality of Life in Differentiated Thyroid Carcinoma Patients

Background: We aimed to study the HRQL in patients with differentiated thyroid carcinoma (DTC) during hypothyroidism due to thyroxin withdrawal, which is induced routinely for iodine-131 (I-131) whole body scan and ablative treatment. Methods: Between September 2011 and March 2012, eligible patients with DTC who were referred to our institution for diagnostic or therapeutic radioiodine administration under hypothyroid conditions due to thyroid hormone withdrawal were asked to complete the psychological instruments rating their HRQL and psychological status. HRQL was studied using the Short Form (SF-36), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), the total mood disturbance (TMD) score, Beck Depression Inventory (BDI).One hundred and forty three hypothyroid patients with DTC (F=101, M=42, age=58.7 yrs) who were also on low-iodine diet were included in this study. Hypothyroidism was induced by withdrawal of thyroxin replacement in all patients. Results: The results of SF-36 showed that the HRQL was significantly impaired in hypothyroid patients during withdrawal of thyroxin (physical component scale: 44.3 ± 9.5, mental component scale: 40.8 ± 10.2, p ≤ 0.001). Depression scores were in the normal or non-clinically relevant range: 4.1 ± 3.8 on the HADS-Depression and 8.3 ± 6.6 on the Beck Depression Index. However, the mean score of 28.8 ± 25.2 on the POMS TMD was within normal range. Conclusion: HRQL is impaired in hypothyroid patients with DTC during thyroxine withdrawal before I-131 whole body scan and radioiodine therapy.

Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer.

Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 ± 2.3 ng/mL vs. 6.2 ± 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation.

Practice trends in patients with persistent detectable thyroglobulin and negative diagnostic radioiodine whole body scans: a survey of American Thyroid Association members.

Management of patients with thyroglobulin (Tg)-positive/scan-negative thyroid cancer remains challenging. American Thyroid Association (ATA) guidelines recommend potential use of empiric (131)I therapy and various scanning modalities, but no standard for managing such cases exists. We surveyed ATA members to assess current practice in management of patients with Tg-positive/scan-negative disease. Members participated in a web-based survey of six case scenarios of Tg elevations but iodine scan negativity. A total of 288 ATA members (80% male) participated. Patient age, sex, and basal and stimulated Tg varied between the cases. Respondents were asked their opinion regarding empiric (131)I therapy use, including (131)I dose, use and duration of low-iodine diet, thyroxine withdrawal or recombinant human thyrotropin (rhTSH), and utilization of additional imaging (neck ultrasound (US) or positron emission tomography/computed tomography (PET/CT)) and reconsideration of (131)I therapy. Between 16% and 51% recommended initial use of empiric (131)I for the various scenarios. The majority chose a (131)I dose between 75 and 150 mCi, and 73% employed a low-iodine diet for two or more weeks. Preference between thyroxine withdrawal versus rhTSH was evenly split. More than 98% obtained a neck US if empiric (131)I was not given; 52-89% would proceed to PET/CT if US was negative. Only 44% used rhTSH stimulation in PET scan preparation. (131)I use was more common with stimulated Tg significantly >10 ng/mL. (131)I therapy was slightly more likely with PET-positive (56%) than PET-negative status (45%). Respondents were split regarding empiric (131)I if basal and stimulated Tg increased ≥150% over two years. Providers in North America less commonly utilized (131)I treatment than those from other areas. In the face of possible heterophilic antibody interference in the Tg assay, the majority did not recommend (131)I therapy. Empiric (131)I therapy is still utilized for patients with Tg-positive/scan-negative disease. Neck US is frequently used to further evaluate such cases as (18)FDG-PET/CT, albeit the latter is used somewhat less often. Use of (131)I therapy correlated with the degree of Tg elevation or development of Tg antibodies, and was recommended more commonly with PET-positive than PET-negative status in patients with lower Tg levels. (131)I was less commonly used by providers within North America.

Risk factors for developing hyponatremia in thyroid cancer patients undergoing radioactive iodine therapy.

BackgroundDue to the alarming increase in the incidence of thyroid cancer worldwide, more patients are receiving postoperative radioactive iodine (RAI) therapy and these patients are given a low-iodine diet along with levothyroxine withdrawal to induce a hypothyroid state to maximize the uptake of RAI by thyroid tissues. Recently, the reported cases of patients suffering from life-threatening severe hyponatremia following postoperative RAI therapy have increased. This study aimed to systematically assess risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients.MethodsWe reviewed the medical records of all thyroid cancer patients who underwent thyroidectomy and postoperative RAI therapy from July 2009 to February 2012. Demographic and biochemical parameters including serum sodium and thyroid function tests were assessed along with medication history.ResultsA total of 2229 patients (47.0±11.0 years, female 76.3%) were enrolled in the analysis. Three hundred seven patients (13.8%) of all patients developed hyponatremia; 44 patients (2.0%) developed moderate to severe hyponatremia (serum Na+≤130 mEq/L) and another 263 (11.8%) patients showed mild hyponatremia (130 mEq/L<serum Na+≤135 mEq/L). In univariate analysis, old age, female sex, presence of hypertension, presence of diabetes, use of thiazide diuretics, use of angiotensin receptor blocker or angiotensin-converting enzyme inhibitors, lung metastasis, and hyponatremia and lower estimated glomerular filtration rate at the start of RAI therapy were significantly associated with hyponatremia in patients undergoing RAI therapy after total thyroidectomy. Multivariate analysis showed that old age, female sex, use of thiazide diuretics, and hyponatremia at the initiation of RAI therapy were independent risk factors for the development of hyponatremia.ConclusionOur data suggest that age greater than 60 years, female sex, use of thiazide, and hyponatremia at the initiation of RAI therapy are important risk factors for developing hyponatremia following RAI therapy in post-thyroidectomy patients.

Low iodine diet for one week is sufficient for adequate preparation of high dose radioactive iodine ablation therapy of differentiated thyroid cancer patients in iodine-rich areas.

Most current guidelines suggest one or two weeks of low iodine diet (LID) before radioactive iodine ablation therapy (RAIT) to increase its efficacy in differentiated thyroid cancer (DTC) patients after total thyroidectomy. LID duration is particularly important for patients living in iodine excess areas. However, there is no standardized LID protocol and there are limited reports regarding the relationship between LID and ablation outcome. Therefore, we aimed to evaluate the optimal LID duration and define clinical features that affect ablation outcome. A total of 202 papillary thyroid cancer patients with total thyroidectomy preparing for RAIT were enrolled. All patients had undergone two weeks of LID before (131)I administration. Morning spot urine specimens were obtained twice (one week or two weeks after LID, respectively) from each patient. Urine iodine excretion (UIE) values were used to evaluate LID efficacy. Successful ablation was defined using two definitions: (i) no visible uptake on a follow-up diagnostic (131)I scans, and (ii) no visible uptake on a follow-up diagnostic (131)I scans and stimulated serum thyroglobulin (Tg) levels <1 ng/mL. The UIE median values after LID for one and two weeks were lower than 50 μg/L, and the median UIE values were not significantly different according to the LID duration. Based on the first criterion for successful ablation, 175 of the 195 patients were successfully ablated. There were no significant differences in mean and median UIE levels between the ablated and non-ablated groups after LID for two weeks. The rate of ablation did not differ between the mild and moderate iodine deficient groups. Based on the second criterion for successful ablation, 149 of 188 patients were successfully ablated. The ablation success rate did not differ between UIE levels. When we analyzed clinical factors that affect ablation outcome, serum Tg level at the time of ablation was the only significant variable in multivariate logistic analysis. Strict LID for one week was sufficient to achieve target UIE values for RAIT preparation, even in iodine-rich areas.

The Impact of Iodinated Contrast Agent Administered During Preoperative Computed Tomography Scan on Body Iodine Pool in Patients with Differentiated Thyroid Cancer Preparing for Radioactive Iodine Treatment

Iodine in iodinated contrast agents (ICAs) interferes with radioactive iodine treatment (RAIT) and diagnostic scans in patients with differentiated thyroid carcinoma (DTC) because it can compete with ¹³¹I. Published guidelines recommend delaying RAIT for three to four months in patients who have been exposed to ICA. Spot urinary iodine concentration is a useful marker to reflect the body iodine pool. We investigated the impact of ICAs administered at preoperative computed tomography (CT) scan on the body iodine pool to determine the proper time interval between preoperative CT and RAIT in DTC patients. We performed a retrospective review of 1023 patients with DTC who underwent a preoperative CT scan with ICA, total thyroidectomy, and one week of low-iodine diet in preparation for RAIT. Urine iodine excretion (UIE) was measured in spot urine by inductively coupled plasma mass spectrometry and reported both in simple concentration (μg/L) and divided by gram creatinine (μg/gCr). Patients were divided into five groups by time interval in days between preoperative CT scan and spot urine iodine measurement (A, 31-60 [n=29]; B, 61-90 [n=155]; C, 91-120 [n=546]; D, 121-150 [n=226]; E, 151-180 [n=67]). The median (interquartile range) of UIE (μg/gCr) in each group was 44.4 (27.7-73.2) in group A, 33.3 (22.8-64.7) in group B, 32.7 (20.8-63.0) in group C, 32.0 (20.6-67.0) in group D, and 30.4 (19.6-70.8) in group E. There was no significant difference between group A and the remaining groups (p>0.05) Also, the proportion of patients who achieved the appropriate UIE for RAIT according to our hospital's cutoff (≤66.2 μg/gCr) was not different between groups (A, 72.4%; B, 76.1%; C, 77.5%; D, 74.8%; E, 74.6%) (p=0.78). This study shows that a UIE of one month after preoperative CT scan with ICA was not higher than that of six months after CT scan in patients who underwent total thyroidectomy for DTC. Thus, current guidelines that recommend delay of RAIT for three to four months after CT scan with ICA should be revisited and future studies to clarify the appropriate time interval between CT scan with ICA and RAIT are warranted.

Letter: Diagnostic Whole-Body Scan May Not Be Necessary for Intermediate-Risk Patients with Differentiated Thyroid Cancer after Low-Dose (30 mCi) Radioactive Iodide Ablation (Endocrinol Metab 2014;29:33-9, Eon Ju Jeon et al.).

The initial treatment of differentiated thyroid cancer (DTC) is thyroidectomy, followed by remnant ablation with radioiodine (I-131). However, substantial uncertainty persists over the indications and optimal dose for I-131. In addition, the usefulness of a follow-up diagnostic I-131 whole-body scan (WBS) performed within 6 to 12 months after initial therapy is controversial [1]. Although a diagnostic WBS is not recommended for low-risk patients, it may be of value in the follow-up of patients with high or intermediate risk [2]. Since incidence of DTC and patients who undergo remnant ablation has been increasing rapidly, these issues are interesting and important to clinicians. Jeon and Jung [3] demonstrated that a postablation diagnostic I-131 WBS in intermediate-risk patients with DTC may not be necessary. Although the authors suggested their study results carefully, in my opinion, below mentioned point need to be emphasized. According to this study, among 255 intermediate-risk patients, 233 had no I-131 uptake in the thyroid bed, and 22 had I-131 uptake on the thyroid bed. On diagnostic WBS, the group showing uptake had significantly higher lymph node metastasis and on average had stimulated thyroglobulin (TG) levels below 2 ng/mL in the absence of TG antibodies. Among the 22 patients showing uptake in the thyroid bed, only five revealed stimulated TG levels above 2 ng/mL. Stimulated TG levels alone did not represent thyroid uptake in a significant portion of patients, and alone was not sufficient to screen patients. Although the recurrence of thyroid cancer was not statistically different between the group with no uptake and the group with uptake in the thyroid bed, the duration of follow-up was short. Moreover, only one among four patients with recurrence showed stimulated TG levels above 2 ng/mL and diagnostic WBS showed no uptake in three patients with DTC recurrence. Prospective, long-term studies on whether patients with or without a thyroid remnant in diagnostic WBS show different prognoses and outcomes will provide important information about this issue. Long-term follow-up data from 17 patients with thyroid bed uptake in this study is expected to provide important information despite the small number of patients. In real practice, the recommended preparatory low-iodine diet before diagnostic WBS is very stressful and bothersome for patients. Therefore, these results by Jeon and Jung [3] will be very valuable data in establishing an evidence-based follow-up strategy for DTC.

Severe Hyponatremia Following Radioactive Iodine Therapy in Patients with Differentiated Thyroid Cancer

Symptomatic hyponatremia in association with radioactive iodine (RAI) therapy for differentiated thyroid cancer has rarely been reported. Due to the increasing incidence of thyroid cancer worldwide, more patients are now receiving postoperative RAI therapy. We report two cases of life-threatening severe hyponatremia in association with RAI therapy. Two elderly female patients who had bilateral thyroidectomies for their thyroid cancer underwent a low-iodine diet and levothyroxine withdrawal for two weeks prior to RAI therapy. Upon admission, the patients were given 130 mCi (4810 MBq) and 150 mCi (5550 MBq) of (131)I respectively, and oral hydration (two to three liters of water daily) to increase the frequency of emptying the bladder of RAI. Both patients completed their RAI therapy without significant complications and were discharged from hospital. Two days after discharge, both patients were admitted to the emergency room with complaints of severe nausea and dizziness. Initial laboratory tests revealed that they were in a hypothyroid state and had severe hyponatremia with a serum sodium level of 108 mEq/L. The symptomatic hyponatremia responded to intravenous hypertonic saline infusion and thyroid hormone replacement, and the patients made a full recovery. The low-iodine diet and hypothyroid state with overzealous hydration in the setting of RAI therapy may have provoked severe hypotonic hyponatremia. Hypothyroid patients after undergoing RAI therapy, especially the elderly, are at an increased risk for serious hyponatremia and should be monitored closely.

Decreased Expression of Hepatic Low-Density Lipoprotein Receptor–Related Protein 1 in Hypothyroidism: A Novel Mechanism of Atherogenic Dyslipidemia in Hypothyroidism

The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins. In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of 3,3',5-triiodo-L-thyronine (T3) treatment on hepatic LRP1 expression. C57BL/6 mice were fed a normal diet (control group) or a low-iodine diet supplemented with 0.15% propylthiouracil (PTU/LI group) for 4 weeks. Mice in the PTU/LI group were injected intraperitoneally with T3 (0, 30, and 150 μg/kg of body weight) for 7 days. HepG2 cells were incubated in fetal bovine serum or charcoal-stripped fetal bovine serum with various concentrations of T3. The expression and function of LRP1 in liver samples and cells were analyzed. Hypothyroidism was successfully induced in PTU/LI mice. Hepatic LRP1 protein expression was lower in the PTU/LI group than in the control group. T3 treatment upregulated hepatic LRP1 protein expression in PTU/LI mice. LRP1 expression in HepG2 cells was reduced after incubation in the medium containing charcoal-stripped fetal bovine serum, which mimics hypothyroidism in vitro, and was recovered by T3 treatment. The protein expression of LRP1 in HepG2 cells was increased by T3 treatment in a dose-dependent manner up to 2.0 nM T3. However, LRP1 mRNA transcription was not affected by hypothyroidism conditions or T3 treatment, either in liver samples or in HepG2 cells. T3 treatment on HepG2 cells increased cellular uptake of lipid-conjugated apolipoprotein E through LRP1. Our data demonstrate that hepatic LRP1 expression and function decrease in hypothyroidism and are regulated by the thyroid hormone. These results suggest that in hypothyroidism, decreased expression of hepatic LRP1 may be associated with reduced clearance of circulating remnant lipoproteins.

Association Between Excessive Urinary Iodine Excretion and Failure of Radioactive Iodine Thyroid Ablation in Patients with Papillary Thyroid Cancer

A low-iodine diet (LID) is usually recommended for a week or two before radioactive iodine (RAI) ablation therapy in papillary thyroid cancer (PTC) patients after total thyroidectomy. However, it is still controversial whether an LID affects ablation outcomes. We therefore evaluated the association between urinary iodine excretion and the rate of successful ablation and investigated the determinants of successful RAI ablation outcomes. We retrospectively reviewed the records of 295 consecutive patients with PTC who received 1110 MBq RAI remnant ablation therapy with thyroid hormone withdrawal after total thyroidectomy. Successful ablation was defined as either no visible or faint uptake on a follow-up scan (definition 1), or no visible or faint uptake on a follow-up scan and a stimulated thyroglobulin level <2 ng/mL (definition 2). The proportion of patients with appropriate LID status (defined as a urinary iodine concentration [UIC] <66.2 μg iodine/g creatinine [μg/gCr]) was significantly higher in the successfully ablated group (81% vs. 67%, p=0.03). Based on definition 1, 80.3% (237/295) of patients were successfully ablated. The ablation rate was significantly lower in patients who had a UIC >250 μg/gCr at the time of RAI ablation (p<0.05). In multivariate analysis, a UIC >250 μg/gCr was the only significant variable associated with ablation failure (p=0.002, odds ratio [OR] 4.74 [95% confidence interval (CI) 1.78-12.63]). Based on definition 2, 74.9% (221/295) of patients were successfully ablated. A UIC >250 μg/gCr at RAI administration showed a significant association with ablation failure (p<0.05). The OR of a UIC >250 μg/gCr for ablation failure was 3.88 [CI 1.42-10.57] (p=0.008). Excessive iodine intake (UIC >250 μg/gCr) was associated with poor RAI ablation outcomes. Because this amount of iodine is very high, we propose that the level of strictness of the LID protocol should be modified according to the region that the patient is from and the food that the patient is accustomed to eating. Even in those areas where iodine intake is high, overly strict compliance with an LID protocol is not necessary and simple recommendations to avoid iodine-rich foods would be appropriate.

Effects of High Fluoride and Low Iodine on Thyroid Function in Offspring Rats

Thirty-two Wistar rats were divided randomly into four groups of eight with six females and two males in each group. The rats were exposed to high fluoride drinking water (45 mg F− L−1 from 100 mg NaF L−1), low dietary iodine (0.0855 mg kg−1), or both together in order to assess the effects of these three regimens on the thyroid function of the offspring rats. After the animal model was established, the offspring rats were bred and 10-, 20-, 30-, 60-, and 90-d-old rats were used for the experiment. The treatments for the offspring rats were the same as those of their parents. In comparison with control rats, the relative thyroid glands were changed by three regimens, but the mean values of thyroid weight in the experimental groups saw no marked difference. Serum TT3 levels were increased in all stages in the low iodine (LI) group. In the high fluoride (HiF) group, increase in TT3 levels was observed except in 20-d-old rats. Decrease in TT3 at 20- and 90-d and increase in TT3 at 30- and 60-d were found in HiF+LI group. Serum TT4 levels first saw an increase, and then dropped in the LI and HiF+LI group. However, an increase in TT4 was found in the HiF group. The levels of TSH in serum rocketed at d 20, and then dropped in the next stages in experimental groups. The results suggested that thyroid disorder could be induced by high flroride in drinking water, low iodine diet, or both of them. Exposure time to fluoride or low iodine diet was one of the important factors that fluoride can induce the development of thyroid dyfunction.