Twenty-four hour urinary sodium and potassium excretion in adult population of Slovenia: results of the Manjsoli.si/2022 study.

OBJECTIVE: The objective of study was to assess 24-h urinary Na and K excretion and estimate the average salt and K intakes in a nationally representative sample of the adult population of Slovenia. DESIGN: A nationally representative cross-sectional study was conducted in four stages between September and November 2022: study questionnaire, physical measurements, 24-h urine collection and laboratory analysis. SETTING: Slovenia. PARTICIPANTS: We invited 2000 adult, non-institutionalised inhabitants of Slovenia, aged between 25 and 64 years. A stratified two-staged sample was selected from this population by the Statistical Office of Slovenia, using sampling from the Central Population Register. According to the WHO methodology, additional eligibility criteria were screened before participating. A total of 518 individuals participated in all four stages of the study, resulting in a response rate of 30 %. RESULTS: The mean 24-h urinary Na excretion was 168 mmol/d (95 % CI 156, 180), which corresponds to a mean estimated intake of 10·3 g salt/d (95 % CI 9·6, 11·1). Mean 24-h urinary K excretion was 65·4 mmol/d (95 % CI 63·2, 67·5), and the estimated mean K intake was 2·93 g/d (95 % CI 2·84, 3·03). There were statistically significant differences in mean intakes between males and females. The mean sodium-to-potassium ratio was 2·7 (95 % CI 2·5, 2·8). CONCLUSIONS: The study results highlighted that the salt intake in the adult population of Slovenia remains much higher than recommended by the WHO, and K intakes are insufficient, as most participants did not meet the recommendations.

[111In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS: A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 µg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS: Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 µg and 50 µg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION: In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Semaglutide delays 4-hour gastric emptying in women with polycystic ovary syndrome and obesity.

AIM: To evaluate the effect of once-weekly subcutaneous semaglutide 1.0 mg on the late digestive period of gastric emptying (GE) after ingestion of a standardized solid test meal by using technetium scintigraphy, the reference method for this purpose. METHODS: We conducted a single-blind, placebo-controlled trial in 20 obese women with polycystic ovary syndrome (PCOS; mean [range] age 35 [32.3-40.8] years, body mass index 37 [30.7-39.8] kg/m2 ) randomized to subcutaneous semaglutide 1.0 mg once weekly or placebo for 12 weeks. GE was assessed after ingestion of [99mT c] colloid in a pancake labelled with radiopharmaceutical by scintigraphy using sequential static imaging and dynamic acquisition at baseline and at Week 13. Estimation of GE was obtained by repeated imaging of remaining [99mT c] activity at fixed time intervals over the course of 4 hours after ingestion. RESULTS: From baseline to the study end, semaglutide increased the estimated retention of gastric contents by 3.5% at 1 hour, 25.5% at 2 hours, 38.0% at 3 hours and 30.0% at 4 hours after ingestion of the radioactively labelled solid meal. Four hours after ingestion, semaglutide retained 37% of solid meal in the stomach compared to no gastric retention in the placebo group (P = 0.002). Time taken for half the radiolabelled meal to empty from the stomach was significantly longer in the semaglutide group than the placebo group (171 vs. 118 min; P < 0.001). CONCLUSION: Semaglutide markedly delayed 4-hour GE in women with PCOS and obesity.

18F-choline PET/CT for parathyroid scintigraphy: significantly lower radiation exposure of patients in comparison to conventional nuclear medicine imaging approaches.

BACKGROUND: Parathyroid subtraction scintigraphy (PSS) is the most commonly used imaging method for localisation of hyperfunctioning parathyroid glands (HPGs) in primary hyperparathyroidism (PHP), a common endocrine disorder. Hybrid (SPECT/CT) imaging with 99mTc-sestaMIBI (MIBI) at an early and delayed phase (dual-phase imaging) may be the most accurate conventional imaging approach, but includes additional radiation exposure due to added CT imaging. Recently, 18F-choline (FCH) PET/CT was introduced for HPG imaging, which can also be performed using the dual-phase approach. To date, no studies have compared organ doses and the effective dose (ED) from conventional subtraction scintigraphy, dual-phase MIBI SPECT/CT, and FCH PET/CT in the localisation of HPGs. AIM: In addition to the comparison of the diagnostic performance of FCH PET/CT and conventional scintigraphic imaging methods, the aim of the study was to measure the organ doses and the ED for conventional subtraction parathyroid imaging protocols, using dual-phase MIBI SPECT/CT as a potential conventional imaging method of choice and FCH dual-phase PET/CT as a potential future imaging method of choice for the localisation of HPGs. Materials, methods. Thirty-six patients referred for parathyroid imaging with a clinical indication of PHP underwent preoperative PSS and dual-phase SPECT/CT imaging with the addition of FCH PET/CT. The diagnostic performance of the imaging modalities was assessed by using histology results as a gold standard. Radiation exposure was calculated for the administered activities of radiopharmaceuticals using ICRP80 weighting factors and for CT exposure at hybrid imaging using dose-length products and the ImPACT CT Patient Dosimetry Calculator. RESULTS: The diagnostic performance of FCH PET/CT was significantly better than that of conventional imaging modalities (sensitivity of 97% vs 64% and 46% for MIBI SPECT/CT and PSS, respectively, with comparable specificity of over 95% for all modalities). The highest radiation exposure was caused by conventional PSS (7.4 mSv), followed by dual-phase MIBI SPECT/CT (6.8 mSv). The radiation exposure was the lowest for dual-phase FCH PET/CT imaging (2.8 mSv). The added CT imaging for both hybrid approaches did not cause significant additional radiation exposure (1.4 mSv for MIBI SPECT/CT, additional 26.4% to overall exposure; 0.8 mSv for FCH PET/CT, additional 42.4% to overall exposure). CONCLUSION: In comparison to conventional scintigraphic imaging of HPGs, emerging hybrid (SPECT/CT, PET/CT) imaging techniques combine superior diagnostic performance with lower radiation exposure to patients.

Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample.

PURPOSE: The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. METHODS: Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. RESULTS: The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p < 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p < 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. CONCLUSION: PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression.

Carotid Artery Stiffness, Digital Endothelial Function, and Coronary Calcium in Patients with Essential Thrombocytosis, Free of Overt Atherosclerotic Disease.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) are at increased risk for atherothrombotic events. Our aim was to determine if patients with essential thrombocytosis (ET), a subtype of MPNs, free of symptomatic atherosclerosis, have greater carotid artery stiffness, worse endothelial function, greater coronary calcium and carotid plaque burden than control subjects. PATIENTS AND METHODS: 40 ET patients without overt vascular disease, and 42 apparently healthy, age and sex-matched control subjects with comparable classical risk factors for atherosclerosis and Framingham risk of coronary disease were enrolled. All subjects were examined by physical and laboratory testing, carotid echo-tracking ultrasound, digital EndoPat pletysmography and CT coronary calcium scoring. RESULTS: No significant differences were found between ET patients and controls in carotid plaque score [1 (0-1.25) vs. 0 (0-2), p=0.30], ß- index of carotid stiffness [7.75 (2.33) vs. 8.44 (2,81), p=0.23], pulse wave velocity [6,21 (1,00) vs. 6.45 (1.04) m/s; p=0.46], digital reactive hyperemia index [2.10 (0.57) vs. 2.35 (0.62), p=0.07], or augmentation index [19 (3-30) vs. 13 (5-22) %, p=0.38]. Overall coronary calcium burden did not differ between groups [Agatston score 0.1 (0-16.85) vs. 0 (0-8.55), p=0.26]. However, significantly more ET patients had an elevated coronary calcium score of >160 [6/40 vs. 0/42, p < 0.01]. CONCLUSIONS: No significant differences between groups were found in carotid artery morphology and function, digital endothelial function or overall coronary calcium score. Significantly more ET patients had an elevated coronary calcium score of >160, indicating high cardiovascular risk, not predicted by the Framingham equation.

An Advantageous Role of Spectral Doppler Sonography in the Evaluation of Thyroid Dysfunction During the Postpartum Period.

OBJECTIVES: To evaluate the diagnostic value of spectral Doppler sonography in women with thyroid dysfunction during the first postpartum year. METHODS: This prospective observational clinical study included 83 consecutive untreated women: 32 with hyperthyroid postpartum thyroiditis, 32 with hypothyroid postpartum thyroiditis, and 19 with Graves disease, which first appeared within 12 months after delivery. Thyrotropin, free thyroid hormones, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were measured. With a 7.5-MHz linear transducer, we measured the thyroid volume and peak systolic velocity (PSV) at the level of intrathyroid arteries. RESULTS: Hyperthyroid postpartum thyroiditis appeared significantly earlier (mean ± SD, 4.4 ± 1.9 months after delivery) than hypothyroid postpartum thyroiditis (6.5 ± 2.1 months) and Graves disease (7.2 ± 2.7 months; P< .001). The thyroid volume in hyperthyroid postpartum thyroiditis (9.7 ± 6.3 mL) was significantly lower than in hypothyroid postpartum thyroiditis (14.7 ± 10.2 mL; P = .030) and Graves disease (19.4 ± 10.2 mL; P< .001). The PSV in hyperthyroid postpartum thyroiditis (9.4 ± 3.4 cm/s) was significantly lower than in hypothyroid postpartum thyroiditis (14.4 ± 3.9 cm/s; P < .001) and Graves disease (19.8 ± 7.0 cm/s; P < .001). With a cutoff level of 15 cm/s, the sensitivity and specificity of the PSV as a predictor of the correct diagnosis in hyperthyroid postpartum women were 94.7% and 96.8%, respectively. A multinomial logistic regression revealed PSV and the time after delivery at which the disorders presented as independent predictors of the differentiation between hyperthyroid postpartum thyroiditis and Graves disease (P = .003; P = .022). CONCLUSIONS: Spectral Doppler sonography was shown to be a useful and accurate method for thyroid dysfunction evaluation during the postpartum period.

Benign Solid Thyroid Nodules: US-guided High-Intensity Focused Ultrasound Ablation-Initial Clinical Outcomes.

PURPOSE: To assess the short-term efficacy and safety of ultrasonographically (US)-guided high-intensity focused ultrasound (HIFU) ablation for treatment of benign solid thyroid nodules. MATERIALS AND METHODS: This prospective study was approved by the institutional ethics committee, and written informed consent was acquired. HIFU ablation was performed in one session with US guidance and conscious sedation in 20 euthyroid patients (mean age, 44.5 years) with a benign solitary or dominant thyroid nodule. Thyroid nodule volume, US structure, and Doppler pattern were assessed at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Adverse events associated with HIFU were evaluated. Statistical analysis was conducted by using repeated measures analysis of variance, the Student t test, χ(2) test, and correlation analysis. RESULTS: The mean ± standard deviation nodule volume was 4.96 mL ± 2.79 at the start of the study. Nodule volume had decreased to 3.05 mL ± 1.96 at the 3-month follow-up examination (n = 20, P < .001), and reached 2.91 mL ± 2.43 by the 6-month follow-up examination (n = 16, P < .001). By then, the mean volume reduction was 48.7% ± 24.3 (P < .001). Isoechoic nodules showed greater reduction at 1 month than did hypoechoic nodules (31.6% ± 18.1 vs 16.4% ± 8.6, P = .053). Nodules with markedly increased blood flow showed smaller volume reduction at 3 months than did less-vascularized nodules (10.9% ± 14.5 vs 41.5% ± 20.3, P = .054). Minor transient complications (eg, subcutaneous edema, mild skin redness) were observed in two patients. CONCLUSION: Early data suggest that US-guided HIFU ablation is an effective and safe procedure for treatment of benign solid thyroid nodules. Initial US echogenicity and vascularization influence the ablation outcome.

US-guided high-intensity focused ultrasound as a promising non-invasive method for treatment of primary hyperparathyroidism.

OBJECTIVES: To investigate the long-term efficacy and safety of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) treatment in patients with primary hyperparathyroidism (PHPT). METHODS: In our prospective study, 13 of 72 screened patients with PHPT were eligible for HIFU treatment, which was performed in one or two sessions. Parathyroid adenoma size and function were evaluated at baseline, 1, 3, 6, 9, and 12 months after the final HIFU session. RESULTS: In 11 females and 2 males, mean age 55.2 ± 12.41 years, the mean applied energy was 15.2 ± 7.7 kJ. Parathyroid size and parathyroid hormone decreased significantly one month after HIFU therapy (p < 0.002 and p < 0.02, respectively). Calcium concentration decreased slowly to reach significant reduction nine months later (p < 0.05). Complete remission was noted in three patients (23%) after one year, good disease control was achieved in nine (69%), and procedure was unsuccessful in one patient (8%). Number of sessions was significantly related to treatment success (p < 0.05). Transitory side effects were impaired vocal cord mobility in three patients (23.1%), subcutaneous oedema in three patients (23.1%), and a combination of both in two patients (15.4%). CONCLUSIONS: HIFU is a promising non-invasive technique for PHPT treatment, which could serve as therapeutic alternative for selected patients. KEY POINTS: US-guided HIFU is a new non-invasive ablative technique for parathyroid adenomas. The method is efficient and ensures good disease control in most patients. HIFU is a good alternative for patients not meeting surgery criteria. Treatment is well-tolerated with only transient side effects.

Characteristics of exposure to radioactive iodine during a nuclear incident.

BACKGROUND: During a nuclear accident, numerous products of nuclear fission are released, including isotopes of radioactive iodine. Among them is iodine-131, with a half-life of 8.02 days, which emits ß radiation. For decades, it has been effectively and safely used in medicine. However, in the event of a nuclear accident, uncontrolled exposure can have harmful biological effects. The main sources of internal contamination with iodine-131 are contaminated air, food and water. The most exposed organ is the thyroid gland, where radioactive iodine accumulates via the Na+/I- symporter (NIS). NIS does not distinguish between radioactive iodine isotopes and the stable isotope iodine-127, which is essential for the synthesis of thyroid hormones. Exposure to radioactive iodine during a nuclear accident is primarily associated with papillary thyroid cancer, whose incidence begins to increase a few years after exposure. Children and adolescents are at the highest risk, and the risk is particularly significant for individuals living in iodine-deficient areas. CONCLUSIONS: Ensuring an adequate iodine supply is therefore crucial for lowering the risk of the harmful effects of exposure to radioactive iodine at the population level. Protecting the thyroid with potassium iodide tablets significantly reduces radiation exposure, as stable iodine prevents the entry of radioactive iodine into the thyroid. Such protection is effective only within a narrow time window - a few hours before and after the exposure and is recommended only for those under 40 years of age, as the risks of excessive iodine intake outweigh the potential benefits in older individuals.

Subdiaphragmatic activity-related artifacts in myocardial perfusion scintigraphy.

BACKGROUND: Myocardial perfusion imaging (MPI) with single photon emission computed tomography is an established non-invasive technique for assessing myocardial ischemia. This method involves the intravenous administration of a radiopharmaceutical that accumulates in the heart muscle proportional to regional blood flow. However, image quality and diagnostic accuracy can be compromised by various technical and patient-related factors, including high non-specific radiopharmaceutical uptake in abdominal organs such as the stomach, intestines, liver, and gall-bladder, leading to subdiaphragmatic artifacts. These artifacts are particularly problematic for evaluating inferior wall perfusion and often necessitate repeated imaging, which decreases gamma camera availability and prolongs imaging times. CONCLUSIONS: Despite numerous investigated techniques to reduce interfering gastrointestinal activity, results have been inconsistent, and current MPI guidelines provide scant information on effective procedures to mitigate this issue. Based on our experience, some possible approaches to reducing artifacts include choosing stress testing with an exercise stress test, when possible, late imaging, fluid intake, and consuming carbonated water immediately before imaging.

The Effect of Monitored Walking on Extracardiac Intestinal Activity in Myocardial Perfusion Imaging.

Various techniques have been used in attempts to reduce interfering gastrointestinal activity in myocardial perfusion imaging (MPI); however, these approaches have yielded inconsistent results. The goal of this study was to investigate the efficacy of monitored walking, a previously unexplored technique, in reducing subdiaphragmatic activity-related artifacts during pharmacologic stress 99mTc-tetrofosmin MPI with SPECT to improve the overall image quality. Methods: The study included patients who underwent MPI with pharmacologic stress. They were given a step counter immediately after the radiotracer injection and were randomized into a group A, with a request to walk at least 1,000 steps before imaging, and a group B, with no specific instructions about walking. The reconstructed SPECT images were assessed visually. Moderate and severe levels of subdiaphragmatic tracer activity were considered relevant for the interpretation of the scans. Additionally, myocardial and abdominal activity was semiquantitatively assessed on raw planar images, and the mean myocardium-to-abdomen count ratios were calculated. Results: We enrolled 199 patients (95 patients in group A and 104 patients in group B). Clinical characteristics did not differ significantly between the 2 groups. Patients in group A walked more steps than patients in group B (P < 0.001), but there were no differences in the proportion of accepted scans between the 2 groups (P = 0.41). Additionally, there were no differences in the proportion of relevant subdiaphragmatic activity between the groups (P = 0.91). The number of steps did not impact the acceptance rate (P = 0.29). Conclusion: A higher number of steps walked during the waiting period between pharmacologic stress and acquisition does not affect subdiaphragmatic activity-related artifacts or the proportion of accepted scans after pharmacologic stress. However, pedometer use and clear instructions motivate patients to walk while awaiting imaging. Larger studies are required to compare a higher-step-count group with a sedentary control group to assess the influence of walking on gastrointestinal artifacts in MPI.

Diagnosing and management of thyroid nodules and goiter - current perspectives.

Due to the frequent diagnosis of benign thyroid nodules, it is necessary to deviate from the traditional paradigm based on frequent surgical treatment. This article highlights the evolution of diagnosis and treatment in recent years, beginning from standardization of ultrasound assessment of nodules and cytology results to minimally invasive techniques to reduce the size of symptomatic thyroid nodules. These achievements reduce the number of surgeries, enable more individualized care for patients with benign thyroid disease, reduce long-term complications, and promote cost-effectiveness within healthcare systems. Furthermore, although the use of minimally invasive techniques significantly decreases thyroid nodule volume, the thyroid nodule usually does not disappear and the challenges in this field are discussed (the efficacy of thermal ablation, a variable part of thyroid nodules that remains viable after thermal ablation, some of the nodules treated with thermal ablation may require a second treatment over time and the efficacy of thermal ablation in nodules with different phenotypes). However, although surgery still represents the "gold standard" for establishing the final histopathologic diagnosis, it is associated with lifelong thyroid hormone substitution need and serious complications in rare cases. Therefore, it should represent the ultima ratio only after a detailed diagnostic procedure. In the future, artificial intelligence-assisted programs for the evaluation and management of nodules are expected.

Neonatal Thyrotoxicosis in Infants of Mothers with Graves' Disease Treated for Radioiodine-Induced Hypothyroidism: A Literature Review.

Fetal and neonatal thyrotoxicosis occurs in up to 5% of pregnancies in mothers with Graves' disease (GD). This condition is caused by stimulating antibodies against the thyrotropin receptor (TRAbs) that cross the placenta and may stimulate the fetal thyroid, typically in the second half of pregnancy. GD is often treated with radioiodine, resulting in hypothyroidism in most patients, but TRAbs can persist for several years. Even if a pregnant mother is hypothyroid after radioiodine therapy or surgery, her TRAbs can still, although rarely, induce fetal hyperthyroidism. In this review, we first present two cases of neonatal hyperthyroidism in mothers with GD who became hypothyroid after prior radioiodine therapy, identified through a 10-year analysis of the National Perinatal System in Slovenia. Based on these cases, we provide an overview of existing data on this rare clinical condition in neonates. We also discuss the underlying mechanisms and clinical outcomes based on currently available data. In conclusion, our review highlights the importance of careful monitoring during pregnancy in all women with GD, even in those well managed after radioiodine therapy or surgery.

Introduction of a spectrophotometric method for salivary iodine determination on microplate based on Sandell-Kolthoff reaction.

BACKGROUND: Iodine is an essential element for the synthesis of thyroid hormones. Therefore, a reliable marker of iodine supply is important. Iodine is predominantly excreted via kidneys, but also via salivary glands. Our aim was to introduce a new and simple method for determination of salivary iodine concentration (SLIC). MATERIALS AND METHODS: Self-prepared chemicals and standards for Sandell-Kolthoff reaction on microplate with ammonium peroxydisulfate (AP) in the range 0-400 µg/L were used. Suitability of water-based standards (WBS) and artificial saliva-based standards (ASS) for standard curve were tested. We followed standards for method validation, defined concentration of used AP and compared our results with Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: WBS gave more reliable results than ASS as an underestimation of iodine concentration was found for ASS. LoB was 6.5 µg/L, LoD 12.0 µg/L, therefore analytical range was 12-400 µg/L. Intra- and inter-assay imprecisions at iodine concentrations, namely 20, 100, 165, and 350 µg/L were 18.4, 5.1, 5.7, and 2.8%, respectively, and 20.7, 6.7, 5.1, and 4.3%, respectively. Suitable molarity of AP was 1.0 mol/L and showed no difference to 1.5 mol/L (P values for samples with concentration 40, 100, and 150 µg/L, were 0.761, 0.085, and 0.275, respectively), whereas there was a significant change using 0.5 mol/L (P<0.001). Saliva samples could be diluted up to 1:8. There was no interference of thiocyanate and caffeine up to 193.5 mg/L. Our original method was comparable to ICP-MS. Spaerman coefficient was 0.989 (95% CI: 0.984-0.993). CONCLUSIONS: The new method for SLIC determination is in excellent agreement with ICP-MS and easy-to-use.

Thyroid Disorders and Peripheral Arterial Disease.

Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms linking thyroid and cardiovascular disease are known; however, specific clinical complications of peripheral arterial disease as endpoints of clinical trials have not been adequately investigated. The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation, elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation.

Interpreting urinary iodine concentration: effects of urine dilution and collection timing.

OBJECTIVES: In population studies, iodine intake estimation relies on median urinary iodine concentration (UIC). However, interpreting UIC measurements can be challenging. METHODS: In our study, we included 772 adult participants from three groups: nationally representative gender-mixed, women of reproductive age, and pregnant women. We measured UIC and urinary creatinine (U-Cr) to calculate the iodine-to-creatinine ratio (I/Cr). U-Cr cut-off value of 0.226 g/L was used for differentiation between diluted and undiluted urine samples. After excluding samples below this cut-off, new median UIC and I/Cr ratios were calculated. We additionally evaluated the influence of urine sample collection time on UIC. RESULTS: Median UICs were 91.8 µg/L for nationally representative group, 58.3 µg/L for women of reproductive age, and 74.9 µg/L for pregnant women, while I/Cr ratios were 91.7, 102.0, and 159.2 µg/g, respectively. After implementing U-Cr cut-off and excluding all data where U-Cr was below cut-off, new median values were 93.4, 76.3, and 95.4 µg/L for UICs, and 88.6, 88.8, and 128.7 µg/g for I/Cr ratios, respectively. In women of reproductive age, median UIC was significantly lower in urine samples collected after 9:30 and after 12:00 as compared to samples collected before 9.30 (53.4, 57.8, and 97.3 µg/L, respectively). CONCLUSIONS: UIC results should be interpreted with caution, considering urine dilution and sample collection timing. U-Cr measurement should be included in population-based iodine intake studies, with corrections applied especially for pregnant women and younger adults, for whom morning is best for single-spot samples.

Beneficial effects of adequate iodine supply on characteristics of thyroid autonomy.

OBJECTIVE: Our aim was to establish the characteristics of thyroid autonomy (TA) in Slovenian patients and the required therapeutic dose of radioiodine before and ten years after the increase in mandatory salt iodization from previous 10 mg of potassium iodide to 25 mg per kg in 1999 because almost no data about TA and radioiodine treatment with respect to iodine supply are available. DESIGN: Retrospective clinical study. PATIENTS: We reviewed records of all patients referred for the first time in 1998 and 2009 to the Thyroid Department at the University Medical Centre Ljubljana which is a tertiary referral centre with a stable catchment area for more than 20 years. METHODS: TA was diagnosed by thyroid function, ultrasound, scintigraphy and negative TSH receptor antibodies. Demographic characteristics and the applied dose of radioiodine were evaluated. RESULTS: In 1998, significantly more patients presented with TA than in 2009 (383 of 3243, 11·8% and 333 of 4546, 7·3%, respectively, P < 0·001). In 1998, the ratio between hyperthyroid and euthyroid patients was higher than in 2009 (6:1 and 2·1:1, respectively, P < 0·001). In 1998, patients were younger than in 2009 (mean 63·8 ± 13·9 and 66·8 ± 14·9 years, respectively, P < 0·004). Hyperthyroid patients were older than euthyroid in both years (P < 0·001). In 1998, mean applied dose of radioiodine was significantly lower than in 2009 (713 ± 306 and 791 ± 194 MBq, respectively, P = 0·003). CONCLUSIONS: In adequate iodine supply, TA is less frequent, patients are less often hyperthyroid, they are older and cured with higher doses of radioiodine than in mild iodine deficiency.

Efficacy and safety of a 30-day methylprednisolone treatment protocol for subacute thyroiditis: a prospective study.

Objective: The optimal corticosteroid treatment regimen for subacute thyroiditis has not yet been established. To avoid side effects, tapering of the initial dose of corticosteroid is recommended. With reducing dose, the symptoms can recur. Design: In a prospective clinical study, a 30-day methylprednisolone (MPSL) treatment protocol with a starting dose of 24 mg/day and tapered by 4 mg every 5 days was assessed for effectiveness and safety regarding possible adrenal insufficiency. Methods: Fifty-nine patients with subacute thyroiditis were included. At visit 1, after establishing the diagnosis, a short stimulation adrenocorticotrophic hormone (ACTH) test was performed and methylprednisolone treatment was prescribed. At visit 2 (40 ± 5 days after visit 1), clinical, laboratory (including short stimulation ACTH test), and ultrasound evaluation were repeated. Results: Forty-eight patients (81.4%) were cured by the prescribed protocol, having significantly lower cortisol levels after stimulation at visit 1 than patients who were not cured (mean, 674.9 nmol/L and 764.0 nmol/L, respectively, P = 0.012). Seven patients (12.3%) developed adrenal insufficiency; this group had significantly lower cortisol levels after stimulation at visit 1 than patients without adrenal insufficiency development (mean, 561.5 nmol/L and 704.7 nmol/L, respectively, P = 0.005). Using stimulated cortisol level at visit 1 as the explanatory variable, logistic models were optimized to determine treatment efficacy (AUC = 0.745, optimal threshold 729 nmol/L, specificity 71%, sensitivity 73%) and adrenal function (AUC = 0.861, optimal threshold 629 nmol/L, specificity 73%, sensitivity 100%). Conclusions: The described protocol was efficient for more than 80% of patients. Using this protocol, the corticosteroid treatment interval is shorter than proposed in current guidelines. Significance statement: A short but effective protocol for treatment of subacute thyroiditis with methylprednisolone is presented in this article. Using this protocol, the treatment interval is shorter than proposed in current guidelines. Its safety regarding possible adrenal insufficiency is assessed.

Validation of a Spectrophotometric Method for Urinary Iodine Determination on Microplate Based on Sandell-Kolthoff Reaction.

OBJECTIVE: Iodine is an essential part of the thyroid hormones thyroxine and triiodothyronine. Therefore, it is essential to monitor iodine supply in a population. The biochemical marker for assessing and controlling iodine is urinary iodine concentration (UIC). MATERIALS AND METHODS: This cross-sectional study included 180 pregnant women and 308 women of reproductive age. Urine specimens from 185 of the 488 volunteers were used. The urine specimens were measured using 2 methods: (1) ammonium persulfate digestion (APD), followed by the Sandell-Kolthoff (S-K) reaction modified on microplate for spectrophotometric detection; and (2) the reference method, inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The regression equation between the methods was ICP-MS method = 1.137*(APD S-K)-5.57. A Passing-Bablok regression showed no deviation from linearity (P = .17). A Bland-Altman plot showed a negative mean bias of -2.7%. CONCLUSION: The APD S-K reaction modified on microplate for spectrophotometric detection of UIC can be implemented into routine work. Its results are comparable to those of laboratories worldwide and to ICP-MS.