Relevance of plasma lenvatinib concentrations and endogenous urinary cytochrome P450 3A activity biomarkers in clinical practice.

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated. This study investigated the correlation between plasma LEN concentrations and endogenous urinary CYP3A biomarkers in clinical practice. Concentrations of plasma LEN (N = 225) and CYP3A biomarkers (cortisol, 6ß-hydroxycortisol, deoxycholic acid, and 1ß-hydroxydeoxycholic acid) in urine (N = 214) from 20 patients (hepatocellular carcinoma, N = 6; thyroid cancer, N = 3; endometrial cancer, N = 8; and renal cell carcinoma, N = 3) collected for consultation for up to 1 year were evaluated using liquid chromatography-tandem mass spectrometry. Moreover, plasma trough LEN concentrations were predicted using a three-compartment model with linear elimination for outpatients administered LEN before sample collection. Moderate correlations were observed between the quantified actual concentrations and the predicted trough concentrations of LEN, whereas there was no correlation with endogenous urinary CYP3A biomarkers. The utility of endogenous urinary CYP3A biomarkers could not be determined. However, TDM for outpatients administered orally available medicines may be predicted using a nonlinear mixed effect model (NONMEM). This study investigated the utility of endogenous urinary CYP3A biomarkers for personalized medicine and NONMEM for predicting plasma trough drug concentrations. These findings will provide important information for further clinical investigation and detailed TDM.

Analysis of Urinary Iodine Concentration in Differentiated Thyroid Cancer and Breast Cancer Cases.

Iodine intake can affect thyroid and breast cells, and urinary iodine concentration (UIC) is an effective biomarker for iodine intake. OBJECTIVES: This study aimed to analyze the correlation between urinary iodine concentration in differentiated thyroid cancer (DTC) and breast cancer (BC) subjects. METHODS: The study consisted of 80 subjects divided into case (20 DTC and 20 BC subjects) and control (40 subjects). Morning urine or spot urine was used for UIC measurement. RESULTS: In thyroid cancer, UIC median patients and controls were 195.45 ± 133.61 µg/L and 145 ± 39.64 µg/L, respectively, with p =0.33. The UIC median of PTC subjects was significantly higher compared to FTC subjects, 227.12±130.98 µg/L versus 68.75±22.95 µg/L, p=0.00, and papillary thyroid cancer is closely related to a high iodine excretion in urine with contingency coefficient  (c)=0.722. In BC patients, regardless of subtypes, breast cancer subjects showed a significantly lower iodine excretion level. The median of UIC patients and controls were 80.05 ± 38.24 µg/L and 144.25 ± 36.79 µg/L, respectively, p=0.000. CONCLUSIONS: Iodine urine concentrations strongly correlate with the type of DTC histopathology, and in BC subjects, IUC was significantly lower compared to the control.

Long-Term Changes of Urinary Exosomal Peptide Levels After Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational Study.

Background: The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence. Methods: Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared. Results: A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides. Conclusion: Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up. Trial Registration: ClinicalTrials.gov: NCT03488134.

Low-Iodine Diet of 4 Days Is Sufficient Preparation for 131I Therapy in Differentiated Thyroid Cancer Patients.

CONTEXT: No consensus exists about the optimal duration of the low-iodine diet (LID) in the preparation of 131I therapy in differentiated thyroid cancer (DTC) patients. OBJECTIVE: This work aimed to investigate if a LID of 4 days is enough to achieve adequate iodine depletion in preparation for 131I therapy. In addition, the nutritional status of the LID was evaluated. METHODS: In this prospective study, 65 DTC patients treated at 2 university medical centers were included between 2018 and 2021. The patients collected 24-hour urine on days 4 and 7 of the LID and kept a food diary before and during the LID. The primary outcome was the difference between the 24-hour urinary iodine excretion (UIE) on both days. RESULTS: The median 24-hour UIE on days 4 and 7 of the LID were not significantly different (36.1 mcg [interquartile range, 25.4-51.2 mcg] and 36.5 mcg [interquartile range, 23.9-47.7 mcg], respectively, P = .43). On day 4 of the LID, 72.1% of the DTC patients were adequately prepared (24-hour UIE < 50 mcg), and 82.0% of the DTC patients on day 7 (P = .18). Compared to the self-reported regular diet, DTC patients showed a significantly (P < .01) lower percentage of nutrient intake (calories, protein, calcium, iodine, and water) during the LID. CONCLUSION: The 24-hour UIE on day 4 of the LID did not differ from day 7, and therefore shortening the LID from 7 to 4 days seems justified to prepare DTC patients for 131I therapy in areas with sufficient iodine intake and may be beneficial to maintain a sufficient nutritional intake during DTC treatment.

Effect of TSH stimulation protocols on adequacy of low-iodine diet for radioiodine administration.

Low-iodine diet (LID) is a crucial preparation for radioactive iodine (RAI) treatment or scan in thyroid cancer. The aim of this study is to analyze the influence of thyroid stimulating hormone (TSH) stimulation protocols and other clinical factors on LID adequacy. Thyroid cancer patients who underwent LID for RAI scan or treatment were retrospectively analyzed. Patients were guided to have LID for 2 weeks before RAI administration and urine iodine/creatinine ratio (UICR, µg/g Cr) was measured. TSH stimulation was conducted using either thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) injection. Adequacy of LID was classified by UICR as 'excellent (< 50)', 'adequate (50-100)', 'inadequate (101-250)' and 'poor (> 250)'. A total of 1715 UICR measurements from 1054 patients were analyzed. UICR was significantly higher in case of rhTSH use than THW (72.4 ± 48.1 vs. 29.9 ± 45.8 µg/g Cr, P < 0.001). In patients who underwent LID twice using both TSH stimulation protocols alternately, UICR was higher in case of rhTSH than THW regardless of the order of method. Among clinical factors, female, old-age, and the first LID were significant factors to show higher UICR. Although the adequacy of LID was 'adequate' or 'excellent' in most patients, multivariate analysis demonstrated that THW method, male, young age, and prior LID-experience were significant determinants for achieving 'excellent' adequacy of LID. In conclusion, UICR was higher and the proportion of 'excellent' LID adequacy was lower with rhTSH than with THW. UICR was higher also in women, old-age, and LID-naïve patients. Further researches are required to suggest effective methods to reduce body iodine pool in case of rhTSH use and to validate the efficacy of such methods on outcomes of RAI treatment.

Associations between essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid cancer.

Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The concentrations of 10 essential microelements in urine [cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I)] were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1 cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.

A case-control study on the association of mineral elements exposure and thyroid tumor and goiter.

Thyroid tumor and thyroid goiter are prevalent disease around the world. In this case-control study, we investigated the association between exposure to a total of twelve mineral elements and thyroid disease as well as thyroid functions. Participants with thyroid tumor or goiter (N = 197) were matched with a healthy population (N = 197) by age (± 2 years old) and same sex. Questionnaires were used to collect data about the demographic characteristics and information of subjects. Serum and urine samples were collected simultaneously for each of the subjects. Mineral elements, iodine level of urine and levels of the total seven thyroid function indexes in serum were detected respectively. Conditional logistic regression was applied to estimate the associations between mineral elements and the risk of thyroid tumor and goiter through single-element models and multiple-element models. Multiple linear regression was used to evaluate relationships between mineral elements and percentage changes of thyroid functions. Higher concentrations of mineral elements in the recruited population were found in this study than other comparable studies, and the levels of chromium (Cr), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), selenium (Se), antimony (Sb), thallium (Tl) and lead (Pb) in the case group were lower than the control group. According to the single-element models, Cr, Mn, Ni, Sb and Tl showed significant negative associations with the risk of thyroid tumor and goiter, and, Cd showed nonmonotonic dose response. Cd and mercury (Hg) showed a nonmonotonic percentage change with T4, while Tl was associated with the increased FT4 in the control group. Therefore, Cd, Hg and Tl may disturb the balance of thyroid function to some extent, and Cr, Mn, Ni, Cd, Sb, and Tl may become potential influencing factors for the risk of thyroid tumor and goiter.

Urinary Exosomal Thyroglobulin in Thyroid Cancer Patients With Post-ablative Therapy: A New Biomarker in Thyroid Cancer.

Background: Most patients with thyroid cancer typically receive thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation. Exosomes are nanovesicles secreted into extracellular environments, including plasma, saliva, urine, and other body fluids of patients with cancer. We try to find the early prognostic and exosomal biological markers of urine. Methods: We analyzed urinary exosomal proteins, including thyroglobulin and galectin-3, to identify early prognostic biological markers in urine for patients receiving operation and radioactive iodine ablative therapy. We enrolled sixteen newly diagnosed patients with papillary thyroid carcinoma and follicular thyroid carcinoma. We collect all patient's urine samples before operation, immediately after operation, post-operatively at three and six months (4 collections per patient). The levels of pre-operative and post-ablative of U-Ex Tg and galectin-3 in patients with thyroid cancer were measured. Results: Trends in urinary thyroglobulin concentrations in patients with post-ablative thyroid cancer were detected in the first sixteen patients. Importantly, serum thyroglobulin was not detected in five patients after operation and radioactive I-131 ablation, while U-Ex Tg still showed an increasing trend, which implicating the probable recurrence of thyroid cancer. This is the first study to evaluate whether U-Ex Tg is a future biological marker as a substitute for serum thyroglobulin. Conclusion: Our study have developed a brand-new evaluation for tracking thyroid cancer. The most useful scenario in using a test that is potentially more sensitive than existing serological testing is to eliminate the suspicion of recurrence and remove subjects from long term follow up. Trial Registration: ClinicalTrials.gov: NCT02862470; 5, August 2016. https://clinicaltrials.gov/ct2/show/NCT02862470?term=NCT02862470&rank=1. ClinicalTrials.gov: NCT03488134; 3, August 2018. https://clinicaltrials.gov/ct2/show/NCT03488134?term=NCT03488134&draw=2&rank=1.

Urinalysis by combination of the dipstick test and urine protein-creatinine ratio (UPCR) assessment can prevent unnecessary lenvatinib interruption in patients with thyroid cancer.

BACKGROUND: Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein-creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. METHOD: Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. RESULTS: Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. CONCLUSIONS: Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.

Associations of urinary phthalate metabolites with risk of papillary thyroid cancer.

Some studies have revealed thyrotoxicity of phthalates; however, associations of phthalate exposure with papillary thyroid cancer (PTC) remain unclear. We conducted a pair-matching case-control study of 111 PTC cases and 111 age- and sex-matched non-PTC controls to examine associations between urinary concentrations of phthalate metabolites and PTC. Phthalate metabolites were determined in fasting urine specimens by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). After adjusting for potential confounders and other phthalate metabolites, the concentrations of the sum of di (2-ethylhexly) phthalate (DEHP) metabolites in urine were positively associated with PTC [odds ratio (OR) = 5.35; 95% confidence interval (CI): 1.61-17.83], suggesting the effect of phthalates exposure on PTC development. The findings require confirmation.

Effect of the Interaction Between Cadmium Exposure and CLOCK Gene Polymorphisms on Thyroid Cancer: a Case-Control Study in China.

The exposure to endocrine disruptors and the disruption of the circadian rhythms can both affect thyroid hormones, with results that are most likely carcinogenic in humans. The effects of cadmium (Cd) level and circadian-related single-nucleotide polymorphisms (SNPs) on thyroid cancer (TC) risk have rarely been reported. In this study, the associations of urine Cd, CLOCK gene polymorphisms, and TC risk were evaluated, in addition to the effect of the gene-environment interaction on TC risk. In this case-control study, 218 TC cases and 218 controls were enrolled. Cd in urinary samples was determined by atomic absorption spectrometry. Three SNPs (rs3805151, rs3805154, and rs78929565) were genotyped with an improved multiplex ligation detection reaction technique. The individuals with a high Cd level were 1.72-fold more likely to have TC (OR = 1.72, 95%CI 1.04-2.85), and a high Cd level was associated with higher tumor T stage and N stage (OR = 2.42, 95%CI 1.28-4.58; OR = 3.26, 95%CI 1.67-6.33, respectively). Individuals with TT genotype of rs78929565 had a 107 % increase in TC risk (OR = 2.07, 95%CI 1.00-4.29). Cases with CT genotype tended to have a higher AJCC stage (OR = 2.79, 95% CI 1.01-7.78). A significant interaction was detected between the rs78929565 variant and Cd exposure (p interaction = 0.04). The TT genotype carriers of rs78929565 with a high Cd level were more susceptible to thyroid cancer than the major homozygotes carriers who were exposed to a low cadmium level (OR = 2.66, 95%CI 1.07-6.59). These findings suggested that Cd exposure and the CLOCK variant genotypes were associated with TC risk and tumor severity. Individuals with minor allele of rs78929565 and higher Cd exposure had increased susceptibility to TC. Further studies are required to confirm these findings.

Association of exposure to multiple metals with papillary thyroid cancer risk in China.

Papillary thyroid cancer (PTC) has inflicted huge threats to the health of mankind. Metal pollution could be a potential risk factor of PTC occurrence, but existing relevant epidemiological researches are limited. The current case-control study was designed to evaluate the relationships between exposure to multiple metals and the risk of PTC. A total of 262 histologically confirmed PTC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Urine samples were used as biomarkers to reflect the levels of environmental exposure to 13 metals. Conditional logistic regression models were adopted to assess the potential association. Single-metal and multi-metal models were separately conducted to evaluate the impacts of single and co-exposure to 13 metals. The increased concentration of urinary Cd, Cu, Fe, and Pb quartiles was found significant correlated with PTC risk. We also found the decreased trends of urinary Se, Zn, and Mn quartiles with the ORs for PTC. These dose-response associations between Pb and PTC were observed in the single-metal model and remained significant in the multi-metal model (OR25-50th=1.39, OR50-75th=3.32, OR>75th=7.62, p for trend <0.001). Our study suggested that PTC was positively associated with urinary levels of Cd, Cu, Fe, Pb, and inversely associated with Se, Zn, and Mn. Targeted public health policies should be made to improve the environment and the recognition of potential risk factors. These findings need additional studies to confirm in other population.

Intestinal Perforation in ACTH-Dependent Cushing's Syndrome.

Previous studies have linked systemic glucocorticoid use with intestinal perforation. However, the association between intestinal perforation and endogenous hypercortisolism has not been well described, with only 14 previously published case reports. In this study, we investigated if intestinal perforation occurred more frequently in patients with ectopic ACTH syndrome and in those with a greater than 10-fold elevation of 24-hour urinary free cortisol level. Of 110 patients with ACTH-dependent Cushing's syndrome followed in two clinics in Canada, six cases with intestinal perforation were identified over 15 years. Age of patients ranged from 52 to 72, five females and one male, four with Cushing's disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid. Five had diverticular perforation and one had intestinal perforation from a stercoral ulcer. All cases had their lower intestinal perforation when the cortisol production was high, and one patient had diverticular perforation 15 months prior to the diagnosis of Cushing's disease. As in previously reported cases, most had hypokalemia and abdominal pain with minimal or no peritoneal symptoms and this occurred during the active phase of Cushing's syndrome. Whereas all previously reported cases occurred in patients with 24-hour urinary free cortisol levels greater than 10-fold the upper limit of normal when measured and 11 of 14 patients had ectopic ACTH production, only one of our patients had this degree of hypercortisolism and four of our six patients had Cushing's disease. Similar to exogenous steroid use, patients with endogenous hypercortisolism also have a higher risk of intestinal, in particular diverticular, perforation and should be monitored closely for its occurrence with a low threshold for investigation and surgical intervention. Elective colonoscopy probably should be deferred until Cushing's syndrome is under control.

Urinary iodine is increased in papillary thyroid carcinoma but is not altered by regional population iodine intake status: a meta-analysis and implications.

Excessive iodine intake has been associated with increased risk of thyroid cancer (TC) in many studies, but the results have not been consistent. Since it was common knowledge that urinary iodine (UI) is considered a sensitive marker of current iodine intake, we conducted a meta-analysis to clarify the association between high UI and TC. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Cochrane Collaboration. Between-group meta-analyses were performed to compare UI between TC patients and the healthy/euthyroid subjects in local residents and benign thyroid nodules (BTN) patients. Then, between-group meta-analyses to compare the incidence rate of iodine excess were also conducted. The 22 case-control studies included in the meta-analyses represented 15,476 participants. It is the first time to clarify that UI was increased in PTC patients, but was not altered by regional population iodine intake status. Compared with BTN patients, PTC patients exhibited both higher UIC and higher odds ratio of iodine excess only in adequate iodine intake status subgroup; UIC, not the odds ratio of iodine excess, was higher in patients with PTC than those with BTN in above requirements iodine intake subgroup. A novel insight is offered that high UI in PTC patients was less influenced by regional population iodine intake status. It is indicted that high iodine intake is not a risk factor for PTC and high urinary iodine is just a specific characteristic of the disease.

Pattern of urine iodine excretion with low iodine diet during preparation for radioactive iodine ablation in patients with thyroid cancer.

BACKGROUND: The optimal period of low iodine diet during preparation for radioactive iodine (RAI) ablation in an area with iodine-rich diet was investigated. METHODS: Ninety-four patients with thyroid cancer who underwent low iodine diet and RAI were prospectively allocated into 2 groups-thyroxine withdrawal or using recombinant human thyroid stimulating hormone (rhTSH) for TSH stimulation. Their urinary iodine excretion (UIE) patterns were analyzed. RESULTS: There was no clinicopathological difference between the 2 groups except for tumor size and lymph node status. The UIE (median iodine to creatinine ratio, I/Cr) in the withdrawal group on the 7th and 14th day were 18.3 and 17.9 µg/gCr, respectively, with adequate preparation rate of 93.3% on both days (cutoff value 100 µg/gCr). In the rhTSH group, the median I/Cr on the 7th and 14th day were 48.0 and 45.7 µg/gCr (adequate preparation rates 91.8% and 93.8%), respectively. CONCLUSION: One week of low iodine diet is sufficient preparation for RAI regardless of method of TSH stimulation.

A case-control study of urinary levels of iodine, perchlorate and thiocyanate and risk of papillary thyroid cancer.

BACKGROUND: The incidence of thyroid cancer has recently increased worldwide. With the exception of radiation exposure, the effects of potential risk factors on thyroid cancer incidence remain controversial. OBJECTIVES: The association between exposure to iodine, perchlorate, and thiocyanate and papillary thyroid cancer (PTC) incidence was evaluated and risk factors were predicted. METHODS: A pair-matching case-control study was performed including 116 age- and sex-matched PTC cases and 116 non-PTC controls. Iodine, perchlorate, and thiocyanate concentrations in urine specimens were determined by inductively coupled plasma mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. The association between iodine, perchlorate, and thiocyanate urinary concentrations and PTC was evaluated using univariable conditional regression logistic analysis followed by multivariable conditional logistic regression analyses with backward stepwise selection to predict risk factors for PTC. RESULTS: After adjusting for confounders and creatinine standardization, urinary concentrations of iodine [odds ratio (OR) = 11.01, 95% confidence interval (CI): 1.97-30.52] and perchlorate (OR = 2.27, 95% CI: 1.03-5.03) were associated with the risk of PTC, whereas urinary thiocyanate concentration showed a negative association (OR = 0.24, 95% CI: 0.09-0.65). CONCLUSIONS: Increased exposure to iodine and perchlorate may affect PTC development, whereas high thiocyanate exposure may have a beneficial effect.

iTRAQ analysis of urinary proteins: Potential use of gelsolin and osteopontin to distinguish benign thyroid goiter from papillary thyroid carcinoma.

BACKGROUND: Benign thyroid goiter (BTG) and papillary thyroid carcinoma (PTC) are often interchangeably misdiagnosed. METHODS: Pooled urine samples of patients with BTG (n=10), patients with PTC (n=9) and healthy controls (n=10) were subjected to iTRAQ analysis and immunoblotting. RESULTS: The ITRAQ analysis of the urine samples detected 646 proteins, 18 of which showed significant altered levels (p<0.01; fold-change>1.5) between patients and controls. Whilst four urinary proteins were commonly altered in both BTG and PTC patients, 14 were unique to either BTG or PTC. Amongst these, four proteins were further chosen for validation using immunoblotting, and the enhanced levels of osteopontin in BTG patients and increased levels of a truncated gelsolin fragment in PTC patients, relative to controls, appeared to corroborate the findings of the iTRAQ analysis. CONCLUSION: The data of the present study is suggestive of the potential application of urinary osteopontin and gelsolin to discriminate patients with BTG from those with PTC non-invasively. However, this needs to be further validated in studies of individual urine samples.

High Urinary Iodine, Thyroid Autoantibodies, and Thyroid-Stimulating Hormone for Papillary Thyroid Cancer Risk.

Thyroid nodules have become a common clinical problem, and the clinical importance of thyroid nodules lies in the determination of thyroid cancer. This study aims to evaluate the risk factors for papillary thyroid cancer (PTC) with regard to urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in comparison to thyroid nodular goiter (NG). Among the 2041 patients, 43.8% of which showed more than adequate (UIC 200-299 µg/L) and excessive iodine (UIC ≥ 300.0 µg/L) status. Compared with adequate iodine intake, iodine deficiency (UIC < 100 µg/L) was inversely associated with multifocality (OR 0.59, P = 0.040), while more than adequate iodine intake was independently associated with an increased risk of larger tumor size (OR 1.33, P = 0.002) in female PTC patients but not in males. No significant difference in UIC was observed between patients with PTC and NG, suggesting that high iodine intake may be related with the growth of PTC, but not with its oncogenesis. Besides, positive for TPOAb and TGAb were individually associated with papillary thyroid microcarcinoma (PTMC) risk (OR 2.05 and 1.71, respectively, both P < 0.05) in female patients with tumor foci < 1 cm but not in males. Furthermore, younger age (< 46 years), TGAb positivity and small thyroid nodules in both sexes, higher TSH, TPOAb positivity, and multifocality in females could all predict PTC risk (all P < 0.05). These results might have clinical significance for managing patients with thyroid nodules and those with thyroidectomy.

Higher urinary bisphenol A concentration and excessive iodine intake are associated with nodular goiter and papillary thyroid carcinoma.

In the present study, we investigated whether bisphenol A (BPA) levels and excessive iodine intake were associated with papillary thyroid carcinoma (PTC) and nodular goiter (NG). We determined total BPA concentrations (TBC) in paired serum and urine samples, and urinary iodine concentrations (UIC) in urine samples collected from PTC patients, NG patients, and healthy individuals, then compared BPA concentrations and UIC within and between each patient group. The results showed that there were no gender-specific differences in serum TBC and UIC in each group, and no differences across all patient groups. Urinary BPA concentrations (UBC) were higher in the NG and PTC groups compared with the control group. UBC showed gender-specific differences in the NG and PTC group. Furthermore, UIC were higher in the NG and PTC groups compared with the control group. Higher UBC and excessive iodine intake were risk factors for NG and PTC according to multivariate logistic regression analysis. There was a significant correlation between UBC and UIC in each group. These data suggested that higher UBC and excessive iodine intake are associated with NG and PTC. The metabolic and functional pathways between BPA and iodine are potentially linked to the pathogenesis and progression of NG and PTC.