Retrospective Cross-Sectional Study of the Relationship of Thyroid Volume and Function with Anthropometric Measurements, Body Composition Analysis Parameters, and the Diagnosis of Metabolic Syndrome in Euthyroid People Aged 18-65.

Background and Objectives: The thyroid is a key endocrine gland for the regulation of metabolic processes. A body composition analysis (BCA) is a valuable complement to the assessment of body mass index, which is derived only from body weight and height. This cross-sectional retrospective study aimed to investigate the relationships between thyroid volume (TV) and thyroid function parameters, anthropometric measurements, BCA parameters, and the presence of metabolic syndrome (MetS) in adults without clinically overt thyroid disease. Material and Methods: This study involved 45 people (females: 57.8%; MetS: 28.9%) hospitalized for planned diagnostics without signs of acute illness or a deterioration of their health and without thyroid disease, who underwent thyroid ultrasound scans, biochemical tests to assess their thyroid function, MetS assessments, anthropometric measurements, and BCAs using the bioelectrical impedance method. Results: The TV was significantly larger in people with MetS compared to people without MetS. The TV was significantly higher and the serum thyrotropin (TSH) concentration was significantly lower in overweight and obese people than in normal and underweight people. The free triiodothyronine (FT3) serum concentration and TV were correlated with waist circumference and some parameters of the BCA, and the FT3 concentration was also correlated with the body mass index, waist-hip ratio, and waist-height ratio. No significant correlations were found between the FT4 and TSH and the results of the anthropometric and BCA measurements. Conclusions: Even in a population of euthyroid patients without clinically overt thyroid disease, there were some significant relationships between the volume and function of the thyroid gland and the results of their anthropometric parameters, BCAs, and the presence of MetS features.

Flexible MoS2-Polyimide Electrode for Electrochemical Biosensors and Their Applications for the Highly Sensitive Quantification of Endocrine Hormones: PTH, T3, and T4.

Flexibile biosensors have a lot of applications in measuring the concentration of target bioanalytes. In combination with its flexibility, electrochemical sensors containing 2D materials have particular advantages such as enlarged area compatibility, transparency, and high scalability. A flexible biosensor was fabricated by direct synthesis of molybdenum disulfide (MoS2) on a polyimide (PI) substrate, which can be used as the working electrode in electrochemistry platforms. The direct formation of 2D-MoS2 on the PI was achieved using plasma-enhanced chemical vapor deposition (PE-CVD). Since the MoS2 provides higher electrical conductivity, the MoS2-Au-PI flexible sensor is able to provide highly sensitive detection of target proteins with a relatively fast response via cyclic voltammetry. To evaluate the high performance of the fabricated sensor, we selected the endocrine-related hormones parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) as analytes because they are one of the most important markers for the determination of endocrinopathy, however, they are very difficult to quantify. The newly developed biosensor achieved highly sensitive detection of the hormones and could determine their location with high accuracy. In addition, we performed electrochemical measurements of hormones obtained from 30 clinical patients' sera with confirmed agreement and compared with the measurements performed with standard immunoassay equipment (E 170, Roche Diagnostics, Germany).

G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish.

Estrogens act by binding to estrogen receptors alpha and beta (ERα, ERß), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERß mutant embryos but not in GPER mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate was normal in ERα and ERß mutants. We detected gper transcript in discrete regions of the brain and pituitary but not in the heart, suggesting that GPER acts centrally to regulate heart rate. In the pituitary, we observed gper expression in cells that regulate levels of thyroid hormone triiodothyronine (T3), a hormone known to increase heart rate. Compared to wild type, GPER mutants had reduced levels of T3 and estrogens, suggesting pituitary abnormalities. Exposure to exogenous T3, but not estradiol, rescued the reduced heart rate phenotype in gper mutant embryos, demonstrating that T3 acts downstream of GPER to regulate heart rate. Using genetic and mass spectrometry approaches, we find that GPER regulates maternal estrogen levels, which are required for normal embryonic heart rate. Our results demonstrate that estradiol plays a previously unappreciated role in the acute modulation of heart rate during zebrafish embryonic development and suggest that GPER regulates embryonic heart rate by altering maternal estrogen levels and embryonic T3 levels.

TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels.

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology in the hippocampal formation. Overall, 46.4% of the cases were positive for TDP-43 intracellular inclusions, which is consistent with results in other prior community-based cohorts. The pathologies were correlated with hippocampal sclerosis of aging (HS-Aging) linked genotypes. We also assayed brain parenchymal thyroid hormone (triiodothyronine [T3] and thyroxine [T4]) levels. In cases with SLCO1A2/IAPP or ABCC9 risk associated genotypes, the T3/T4 ratio tended to be reduced (p = .051 using 2-tailed statistical test), and in cases with low T3/T4 ratios (bottom quintile), there was a higher likelihood of HS-Aging pathology (p = .025 using 2-tailed statistical test). This is intriguing because the SLCO1A2/IAPP and ABCC9 risk associated genotypes have been associated with altered expression of the astrocytic thyroid hormone receptor (protein product of the nearby gene SLCO1C1). These data indicate that dysregulation of thyroid hormone signaling may play a role in age-related TDP-43 proteinopathy.

Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender.

Background The serum concentration of thyrotropin (TSH) represents a first-line test in diagnostic algorithms. The estimation of TSH reference intervals (RIs) is still a matter of debate due to the high prevalence of subclinical disease making difficult the definition of truly healthy subjects. The aim of this study was to estimate TSH RIs in healthy subjects and to evaluate the effect of age and gender on TSH concentration. Methods Forty-four thousand one hundred and fifty-six TSH data were collected between July 2012 and April 2018 at the Department of Laboratory Medicine, University-Hospital, Palermo. Common and sex-specific RIs were estimated by Arzideh's indirect method after exclusion of individuals younger than 15 years, subjects with repeated TSH tests and with abnormal free thyroxine (fT4), free triiodothyronine (fT3) or anti-thyroid-peroxidase antibodies. The combined effect of age and gender on TSH values was evaluated. Results RIs estimated in the selected individuals (n = 22602) were, respectively, 0.18-3.54 mIU/L (general), 0.19-3.23 mIU/L (men) and 0.18-3.94 mIU/L (women). Women showed significantly higher median TSH than men (1.46 vs. 1.39 mIU/L; p < 0.0001). Both in men and in women, median TSH decreased along with age; however, although up to 60 years in both men and women showed similar values, afterwards women showed constantly higher TSH than men. Accordingly, statistical analysis showed a significant interaction between gender and age (p = 0.001), suggesting that the effect of age on TSH is different between genders. Conclusions Our findings suggest that the indirect method, with appropriate cleaning of data, could be useful to define TSH RIs.

Negative association between free triiodothyronine level and contrast-induced acute kidney injury in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: A low FT3 level is significantly associated with a variety of kidney disease and acute myocardial infarction (AMI). However, it remains unclear whether low FT3 is associated with CI-AKI in patients who underwent pPCI. METHODS: Single-center retrospective study evaluated 363 STEMI patients undergoing pPCI. Patients were classfied into 2 groups, low FT3 group (FT3 < 3.1 pmol/L) and normal FT3 group (FT3 ≥ 3.1 pmol/L);CI-AKI was defined as an increase in the serum creatinine levels of ≥50% or 0.3 mg/dL above the baseline level within 48 h after contrast medium exposure. RESULTS: Overall, 80(22.0%) patients had low FT3, and 59(16.3%) patients developed CI-AKI. The incidence of CI-AKI and in-hospital mortality was significantly higher in patients with low FT3 than normal (31.3% vs 12.0%; 15.0% vs 3.2%, respectively, both p < 0.0001). Multivariate logistic regression analysis indicated that low FT3 was an independent predictor of CI-AKI (odds ratio [OR] = 2.62, 95%CI:1.35-5.07, p < 0.05). In addition, low FT3 was associated with an increased risk of all-cause mortality during a mean follow-up period of 20 months (hazard ratio [HR] = 2.54, 95%CI:1.15-5.60, p < 0.05). CONCLUSION: Low FT3 was associated with CI-AKI, short- and long-term mortality in STEMI patients after pPCI.

A low incidence of iodine-induced hyperthyroidism following administration of iodinated contrast in an iodine-deficient region.

OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study was to determine the incidence of iodinated contrast-induced thyrotoxicosis and to determine whether thyrotoxicosis was more common in patients ≥70 years compared to those <70 years of age. DESIGN: A prospective study of adult patients undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS: Thyroid function tests (TFTs) and urine iodine measurements were performed prior to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from baseline were analysed. RESULTS: A total of 102 patients were included in the final analysis. Overall, TSH levels dropped (P = 0·0002), and free T3 (FT3 ) levels increased (P = 0·04) between baseline and week 4 with normalization by week 8; however, these changes were not considered clinically significant. No significant differences in free T4 (FT4 ) occurred in the overall group (P = 0·82). There were no differences in TFTs between baseline and 4 or 8 weeks for those patients aged <70 compared to ≥70 years. Two patients developed new subnormal TSH values. Of these, one had a 90-mm follicular variant papillary thyroid carcinoma diagnosed while the other had a normal thyroid assessment and TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients developed subclinical hyperthyroidism following a standard dose of iodinated contrast for CT investigations. Given the low incidence of iodine-induced thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid function testing in our region.

Nivolumab-induced thyroid dysfunction.

Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.

Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints.

BACKGROUND: Brominated flame retardants (BFRs) are endocrine disruptors that bioaccumulate in the placenta, but it remains unclear if they disrupt tissue thyroid hormone (TH) metabolism. Our primary goal was to investigate associations between placental BFRs, TH levels, Type 3 deiodinase (DIO3) activity and TH sulfotransferase (SULT) activities. METHODS: Placenta samples collected from 95 women who delivered term (>37 weeks) infants in Durham, NC, USA (enrolled 2010-2011) were analyzed for polybrominated diphenyl ethers (PBDEs), 2,4,6-tribromophenol (2,4,6-TBP), THs (T4, T3 and rT3), and DIO3 and TH SULT activities. RESULTS: PBDEs and 2,4,6-TBP were detected in all placenta samples. PBDEs were higher in placental tissues from male infants compared to female infants, with 2,4,6-TBP and BDE-209 levels approximately twice as high. Among male infants, placental BDE-99 and BDE-209 were negatively associated with rT3 placental levels. For female infants, placental BDE-99 and 2,4,6-TBP were positively associated with T3 concentrations. DIO3 activity was also significantly higher in placental tissues from male infants compared to females, while 3,3'-T2 SULT activity was significantly higher in placental tissues from females compared to males. Among males, several PBDE congeners were positively correlated with T3 SULT, while BDE-99 was negatively associated with T3 SULT among females. Associations generally remained after adjustment for potential confounding by maternal age and gestational age at delivery. CONCLUSIONS: These results suggest BFRs accumulate in the placenta and potentially alter TH function in a sex-specific manner, a possible mechanism to explain the sex-dependent impacts of environmental exposure on children's growth and development. More research is needed to elucidate the effects of BFRs on placenta function during pregnancy, as well as the biological consequences of exposure and thyroid disruption.

Multiple calibrator measurements improve accuracy and stability estimates of automated assays.

OBJECTIVES: The effects of combining multiple calibrations on assay accuracy (bias) and measurement of calibration stability were investigated for total triiodothyronine (TT3), vitamin B12 and luteinizing hormone (LH) using Beckman Coulter's Access 2 analyzer. METHODS: Three calibration procedures (CC1, CC2 and CC3) combined 12, 34 and 56 calibrator measurements over 1, 2, and 3 days. Bias was calculated between target values and average measured value over 3 consecutive days after calibration. Using regression analysis of calibrator measurements versus measurement date, calibration stability was determined as the maximum number of days before a calibrator measurement exceeded 5% tolerance limits. RESULTS: Competitive assays (TT3, vitamin B12) had positive time regression slopes, while sandwich assay (LH) had a negative slope. Bias values for TT3 were -2.49%, 1.49%, and -0.50% using CC1, CC2 and CC3 respectively, with calibrator stability of 32, 20, and 30 days. Bias values for vitamin B12 were 2.44%, 0.91%, and -0.50%, with calibrator stability of 4, 9, and 12 days. Bias values for LH were 2.26%, 1.44% and -0.29% with calibrator stability of >43, 39 and 36 days. Measured stability was more consistent across calibration procedures using percent change rather than difference from target: 26 days for TT3, 12 days for B12 and 31 days for LH. CONCLUSIONS: Averaging over multiple calibrations produced smaller bias, consistent with improved accuracy. Time regression slopes in percent change were unaffected by number of calibration measurements but calibrator stability measured from the target value was highly affected by the calibrator value at time zero.

Aspartate aminotransferase and free thyroid hormones in vaginal washing fluid as markers for preterm pre-labor rupture of membranes.

AIM: To evaluate the diagnostic value of vaginal fluid aspartate aminotransferase (AST), free triiodothyronine (T3) and free thyroxine (T4 ) in women with preterm pre-labor rupture of membranes (PPROM). METHODS: A case-control study was carried out of 100 women: 50 with PPROM (study group) and 50 age-, gestational age- and weight-matched women with intact membranes (control group). All women underwent sterile speculum vaginal examination. The vaginal posterior fornix was irrigated and the retrieved fluid was sent for AST, free T3 and free T4 assays. RESULTS: Median vaginal fluid free T3, free T4 and AST were significantly higher in the PPROM group compared with the control group, with vaginal fluid free T4 having the largest area under the curve on receiver operating characteristic curve analysis (P<0.001). Sensitivity, specificity, positive and negative predictive values for free T3 (cut-off, 1.06 pg/mL) were 88%, 70%, 74.6% and 85.4%, respectively, while those for free T4 (cut-off 0.063 ng/dL) were 86%, 72%, 75.4% and 83.7%, and those for AST (4.5 IU/L) were 56%, 70%, 65.1% and 61.4%, respectively. Vaginal fluid AST had less diagnostic accuracy when compared with either free T3 or free T4. CONCLUSIONS: Vaginal fluid AST, free T3 and free T4 seem to be useful and simple markers in diagnosis of PPROM.

Quantification of thyroxine and 3,5,3'-triiodo-thyronine in human and animal hearts by a novel liquid chromatography-tandem mass spectrometry method.

Assaying tissue T3 and T4 would provide important information in experimental and clinical investigations. A novel method to determine tissue T3 and T4 by HPLC coupled to mass spectrometry is described. The major difference vs. previously described methods lies in the addition of a derivatization step, that is, to convert T3 and T4 into the corresponding butyl esters. The yield of esterification was Ì´ 100% for T3 and 80% for T4. The assay was linear (r>0.99) in the range of 0.2-50 ng/ml, accuracy was in the order of 70-75%, and the minimum tissue amount needed was in the order of 50 mg, that is, about one order of magnitude lower than observed with the same equipment (AB Sciex API 4000 triple quadrupole mass spectrometer) if derivatization was omitted. The method allowed detection of T3 and T4 in human left ventricle biopsies yielding concentrations of 1.51±0.16 and 5.94±0.63 pmol/g, respectively. In rats treated with different dosages of exogenous T3 or T4, good correlations (r>0.90) between plasma and myocardial T3 and T4 concentrations were observed, although in specific subsets different plasma T4 concentrations were not associated with different tissue content in T4. We conclude that this method could provide a novel insight into the relationship between plasma and tissue thyroid hormone levels.

Anti-ruthenium antibodies mimic macro-TSH in electrochemiluminescent immunoassay.

BACKGROUND: Macro-hormones are circulating conjugates of hormones with immunoglobulins, which often artefactually elevate biochemical test results. Particularly when causing only moderate elevation no suspicion will be raised. By far the most frequently encountered macro-hormone is macro-prolactin. Here we report a female patient with rheumatoid arthritis who had persistently and grossly elevated thyroid stimulating hormone (TSH) but normal free thyroxine in electrochemiluminescent assays. Although clinically euthyroid, she was put on thyroxine therapy which caused hyperthyroid symptoms. METHODS: An analytic interference by macro-TSH was assumed by dilution experiments, polyethylene-glycol-precipitation, the addition of a heterophilic antibody blocking reagent and size exclusion chromatography. RESULTS: Further workup, however, revealed the presence of anti-ruthenium antibodies. CONCLUSIONS: To our knowledge this is the first report of anti-ruthenium antibodies selectively interfering with a TSH assay and causing erratic gross elevation of TSH mimicking macro-TSH.

Influence of (99m)Tc-pertechnetate thyroid imaging on radioactive iodine uptake.

OBJECTIVE: To observe the influence of (99m)Tc-pertechnetate on radioactive iodine uptake (RAIU) in patients with Graves' disease (GD) hyperthyroidism after thyroid scintigraphy. METHODS: Totally 40 patients in whom thyrotoxicosis was diagnosed at Peking Union Medical College Hospital from 2013 March to May were recruited, and RAIU were performed in all patients. Gamma-count rates at 1 h,25 h,49 h,73 h and 169 h were examined respectively after intravenous injection of 185 MBq (5mCi)of (99m)Tc-pertechnetate. The counts of (99m)Tc and (131)I as well as effective half-life of (99m)Tc (Teff (99m)Tc) were calculated respectively according to the half-life formula. The ratio of (99m)Tc to background counts (1200) was calculated as a reference value to evaluate biokinetics of (99m)Tc.The relationship between the effective half-life of (99m)Tc(Teff (99m)Tc) and the level of free triiodothyronine (FT3), free thyroxine (FT4), and effective half-life of (131)I (Teff (131)I)were also evaluated. RESULTS: After intravenous injection of (99m)Tc-pertechnetate, (99m)Tc counts at 1h, 25h, 49h, 73h and 169h was (440.16±247.35)×10(4), (11.37±10.67)×10(4), (0.13±0.36)×10(4), (-0.1±0.19)×10(4), respectively, and the ratio of (99m)Tc to background at 1h, 25 h, and 49 h was 3668, 94.75, and 1.08, respectively. The Teff (99m)Tc was (4.41±0.49)h. Inverse correlations were noted between the effective half-life of Teff (131)I and level of FT3 (r=-0.503, P=0.003) and FT4 (r=-0.516, P=0.002), while no significant correlation was found between the Teff (99m)Tc and FT3, FT4 as well as the Teff (131)I. CONCLUSIONS: Teff (99m)Tc is 4.41h, (99m)Tc-pertechnetate thyroid imaging does not influence RAIU three days after injection of (99m)Tc-pertechnetate. Teff (99m)Tc shows no correlation with the thyroid hormone level and RAIU of Graves's hyperthyroidism.

Delta check limits for thyroid function tests adjusted for clinical settings.

BACKGROUND: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings. METHODS: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets. RESULTS: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets. CONCLUSIONS: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs.

Possible link between Hashimoto's thyroiditis and oral lichen planus: a novel association found.

OBJECTIVES: Hashimoto's thyroiditis as well as lichen planus has been associated to a number of disorders, generally of auto-immune origin. A novel possible association between oral lichen planus (OLP) and Hashimoto's thyroiditis (HT) is here proposed on the basis of a cross-sectional survey. MATERIALS AND METHODS: One hundred and five unrelated OLP patients were considered. Diagnosis of HT was based on positive serum anti-TPO, anti-Tg, TSH levels and the typical ultrasound pattern of the thyroid gland. RESULTS: In the present survey, the prevalence of HT in the OLP group was 14.3 % whereas the prevalence of HT-related hypothyroidism in the general population was reported to be equal to 1 %. By Fisher's exact test, it was revealed that the difference between our data and historical prevalence of HT was found statistically significant. CONCLUSION: Actually, there is no definitive hypothesis that could explain the coexistence of OLP and HT. However, considering the onset timing of HT followed by OLP in 93.3 % of our series, we suspected a causal or predisposing role for HT. Specifically, we believe that in HT patients, circulating thyroid antibodies could contribute to trigger an organ-specific auto-immune response also in the oral mucosa or skin, leading to the development of LP lesions. CLINICAL RELEVANCE: Because of the large number of cases of asymptomatic chronic auto-immune thyroiditis, it would be useful that women over 40 years of age affected by OLP were screened for thyroid dysfunction, particularly HT.

Does sunitinib-induced hypothyroidism play a role in the activity of sunitinib in metastatic renal cell carcinoma?

BACKGROUND: The objective of this study was to evaluate if hypothyroidism developing during sunitib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. METHODS: Thirty-one consecutive patients with clear cell mRCC were retrospectively analyzed. Thyroid function was assessed prior to therapy, every 6 weeks during the first 6 months and every 2-4 months thereafter. Hypothyroidism was considered present if thyroid-stimulating hormone (TSH) exceeded the upper normal limit (UNL) with normal triiodothyronine (T3) and thyroxine (T4). RESULTS: Hypothyroidism occurred in 16 patients (52%) within 3 months (range 0.7-22.9) of treatment initiation. Thyroid replacement corrected TSH below the UNL in 10 patients (63%). The distribution according to Motzer prognostic criteria revealed good prognosis in 16 patients (52%), intermediate in 9 (29%) and poor in 6 (19%). The hypothyroid patients tended to have longer progression-free survival (PFS; median 12.2 vs. 9.4 months; p = 0.234) and longer survival (median 22.4 vs. 13.9 months; p = 0.234) than the euthyroid patients. Clinical benefits were similar in both groups. CONCLUSIONS: Hypothyroidism that develops in mRCC patients treated with sunitinib is associated with a trend toward prolonged PFS and survival, with a similar clinical benefit rate.

Thyroid hormones in milk and blood of lactating donkeys as affected by stage of lactation and dietary supplementation with trace elements.

The traditional utilization of donkeys (Equus asinus) as dairy animals has recently attracted substantial scientific interest with regard to human nutrition. Donkey milk is well tolerated by infants with cows' milk allergy, useful in the treatment of human immune-related diseases, in the prevention of atherosclerosis, and in-vitro studies showed an anti-proliferative effect. Active 3-3'-5-triiodothyronine (T3) in colostrum and milk could play different physiological roles, systemic and paracrine, for both the mother and the suckling offspring. The aim was to evaluate whether thyroid hormones (TH) concentrations in milk and blood of lactating donkeys change with the advancing lactation and whether they can be affected by dietary supplementation with several trace elements, some of them directly involved with TH synthesis (I), metabolism (Se) and action (Zn). Sixteen lactating jennies were divided into two groups (CTL and TE). Mixed feed for TE was added with Zn, Fe, Cu, Mn, I, Se and Co. Every 2 weeks milk and blood samples were collected at 11·00. Total concentrations of T3 in milk (T3M) and T3 and T4 in plasma (T3P and T4P) were assayed using ELISA kits, validated for the donkey species. T3M was not correlated with TH concentrations in blood, did not change with the stage of lactation, and was significantly higher in TE (4·09 ± 0·07 ng/ml, mean ± SE) than in CTL group (3·89 ± 0·08 ng/ml). T4P (81·8 ± 5·2 ng/ml) and T3P (15·2 ± 1 ng/ml) significantly changed with time, but were not significantly affected by dietary treatment. T3P/T4P ratio was significantly lower in TE group. This study indicates that in donkey milk the concentration of T3, a human-like bioactive compound, can be affected by trace elements intake.