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.

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.

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.

[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.

Dietary Iron Intake and Biomarkers of Iron Status in Slovenian Population: Results of SI.Menu/Nutrihealth Study.

Inadequate iron intake and iron deficiency are recognised as a public health problem in the population at large, and particularly in specific subpopulations. Dietary iron intake was analysed using data of the national Slovenian food consumption study, SI.Menu (n = 1248 subjects; 10−74 years), while iron status was evaluated with laboratory analyses of blood haemoglobin, serum ferritin, and iron concentration in samples, collected in the Nutrihealth study (n = 280, adults). The estimated daily usual population-weighted mean iron intakes ranged from 16.0 mg in adults and the elderly to 16.7 in adolescents, and were lower in females for all three age groups. The main dietary iron sources in all the age groups were bread and bakery products, meat (products), fruit, and vegetables. The highest prevalence of haemoglobin anaemia was observed in females aged 51−64 years (6.7%). Critically depleted iron stores (ferritin concentration < 15 µg/L) were particularly found in premenopausal females (10.1%). Factors influencing low haemoglobin, ferritin, and iron intake were also investigated. We observed significant correlations between iron status with meat and fish intake, and with iron intake from meat and fish, but not with total iron intake. We can conclude that particularly premenopausal females are the most fragile population in terms of inadequate iron intake and iron deficiency, which should be considered in future research and public health strategies.

Image reconstruction using small-voxel size improves small lesion detection for positron emission tomography.

BACKGROUND: PET/CT imaging is widely used in oncology and provides both metabolic and anatomic information. Because of the relatively poor spatial resolution of PET, the detection of small lesions is limited. The low spatial resolution introduces the partial-volume effect (PVE) which negatively affects images both qualitatively and quantitatively. The aim of the study was to investigate the effect of small-voxel (2 mm in-line pixel size) vs. standard-voxel (4 mm in-line pixel size) reconstruction on lesion detection and image quality in a range of activity ratios. MATERIALS AND METHODS: The National Electrical Manufacturers Association (NEMA) body phantom and the Micro Hollow-Sphere phantom spheres were filled with a solution of [18F]fluorodeoxyglucose ([18F]FDG) in sphere-to-background ratios of 2:1, 3:1, 4:1 and 8:1. In all images reconstructed with 2 mm and 4 mm in-line pixel size the visual lesion delineation, contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR) were evaluated. RESULTS: For smaller (≤ 13 mm) phantom spheres, significantly higher CRC and CNR using small-voxel reconstructions were found, also improving visual lesion delineation. CRC did not differ significantly for larger (≥ 17 mm) spheres using 2 mm and 4 mm in-line pixel size, but CNR was significantly lower; however, lower CNR did not affect visual lesion delineation. CONCLUSIONS: Small-voxel reconstruction consistently improves precise small lesion delineation, lesion contrast and image quality.

Dietary Intake and Status of Vitamin B12 in Slovenian Population.

Vitamin B12 deficiency poses a health concern, especially in vulnerable populations. Dietary vitamin B12 intake was obtained by two 24 h dietary recalls and food propensity questionnaires in a representative Slovenian cross-sectional food consumption survey, SI.Menu (n = 1248 subjects; 10-74 years). For a subgroup of 280 participants, data on serum vitamin B12 were available through the Nutrihealth study. The estimated usual population-weighted mean daily vitamin B12 intakes were 6.2 µg (adults), 5.4 µg (adolescents), and 5.0 µg (elderly). Lower intakes were observed in females. Inadequate daily vitamin B12 intake (<4 µg) was detected in 37.3% of adolescents, 31.7% of adults, and 58.3% elderlies. The significant predictors for inadequate daily vitamin B12 intake were physical activity score in all age groups, sex in adolescents and adults, financial status and smoking in elderly, and employment in adults. Meat (products), followed by milk (products), made the highest vitamin B12 contribution in all age groups. In adolescents, another important vitamin B12 contributor was cereals. The mean population-weighted serum vitamin B12 levels were 322.1 pmol/L (adults) and 287.3 pmol/L (elderly). Low serum vitamin B12 concentration (<148 nmol/L) and high serum homocysteine (>15 µmol/L) were used as criteria for vitamin B12 deficiency. The highest deficiency prevalence was found in elderlies (7.0%), particularly in males (7.9%). Factors associated with high serum homocysteine were also investigated. In conclusion, although vitamin B12 status was generally not critical, additional attention should be focused particularly to the elderly.

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.

Dietary Intake of Folate and Assessment of the Folate Deficiency Prevalence in Slovenia Using Serum Biomarkers.

Folate deficiency is associated with various health issues, including anemia, cardiovascular disease, and birth defects. Low folate intake and suboptimal folate status were found in several countries; however, this topic has not yet been investigated in Slovenia. Dietary folate intake and serum folate status were investigated through the nationally representative food consumption study SI.Menu/Nutrihealth. Folate intake was estimated using a sample of N = 1248 subjects aged 10-74 years, stratified in three age groups (adolescents, adults, elderly population), through two 24 h-dietary recalls and food propensity questionnaire. Data on serum folate and homocysteine was available for 280 participants. Very low folate intake (<300 µg/day) was observed in 59% of adolescents, 58% of adults and 68% of elderlies, and only about 12% achieved the WHO recommended level of 400 µg/day. Major dietary contributors were vegetables and fruit, and cereal products. Living environment, education, employment status and BMI were linked with low folate intake in adults; BMI, and sex in adolescents; and sex in elderlies. Considering low serum folate (<7 nmol/L) and high serum homocysteine (>15 nmol/L), folate deficiency was found in 7.6 and 10.5% in adults and elderlies, respectively. Additional public health strategies should be employed to promote the consumption of folate-rich foods. With current folate intakes, supplementation with folic acid is relevant especially in specific vulnerable populations, particularly in women planning and during pregnancy.

First Estimation of Reference Intervals for Thyroid-Stimulating Hormone and Thyroid Hormones in Slovenian Population.

For thyroid function estimation and clinical decision making, use of appropriate reference intervals for thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) is crucial. For each laboratory, establishment of own reference intervals is advised. For the first Slovenian estimation of reference intervals for thyroid hormones a large group of 1722 healthy individuals without thyroid disease was established retrospectively. Hormone analyses were performed on automated analyser Advia Centaur XP Immunoassay System (Siemens Healthineers), which reference intervals for TSH, fT4 and fT3 were 0.55-4.78 mIU/L, 11.5-22.7 pmol/L, and 3.5-6.5 pmol/L, respectively. Statistical analysis followed non-parametric percentile method. Our laboratory reference intervals for TSH, fT4 and fT3 are mostly narrower than intervals given by manufacturer. Median value, lower and upper limit for TSH, fT4 and fT3 were 1.98 (0.59-4.23) mIU/L, 14.5 (11.3-18.8) pmol/L and 4.82 (3.79-6.05) pmol/L, respectively. Most likely, an inclusion of a high number of healthy individuals without thyroid disease was a reason for such results.

Graves disease and metastatic hormonal-active Hürthle cell thyroid cancer: A case report.

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.

Five-year follow-up and clinical outcome in euthyroid patients with thyroid nodules.

BACKGROUND: Thyroid nodule diagnosis has become increasingly frequent. Defining optimum surveillance intervals for patients with unsuspicious thyroid nodules remains a challenge. This was a single centre cohort study in which patients diagnosed with unsuspicious thyroid nodules in whom no treatment was indicated were invited for re-evaluation 5 years after the diagnosis. The primary end point of the study was to estimate the change in nodule size with thyroid ultrasound (US) and the secondary end point was to assess the need for clinical management 5 years after the diagnosis. PATIENTS AND METHODS: Baseline patient parameters and ultrasound characteristics of the nodules were retrospectively collected. At follow-up, thyroid ultrasound was performed. RESULTS: A hundred and eighteen (107 women / 11 men, aged 56.8 ± 13.4 years) patients were included in the study having 203 nodules at baseline, with mean largest nodule diameter 10.5 ± 7.4 mm. After 5 years, 58 (28.6%) nodules significantly increased in size, 27 (13.3%) decreased, and for 104 (51.2%) of nodules, no change in size was noted. Fourteen (6.9%) nodules disappeared. Additional 26 new nodules (mean largest diameter 7.7 ± 5.0 mm) in 16 patients were identified at follow-up. Regarding the clinical outcome, no new thyroid cancers were found. For 107 (90.7%) patients no further management was indicated. Five (4.2%) patients were referred to thyroidectomy because of the growth of the nodules. Two (1.7%) patients were treated for hyperthyroidism. Four (3.4%) patients did not complete the study. CONCLUSIONS: We report a single centre experience of the natural history of unsuspicious thyroid nodules. Our results showed that 71.4% of such nodules remained stable in size, decreased or even disappeared and that the vast majority of the patients remained clinically stable with no need for treatment 5 years after the diagnosis.

Diagnostic value of [18F]Fluorocholine PET/CT in detection of primary medullary thyroid cancer.

OBJECTIVE: Medullary thyroid cancer (MTC) is a challenging neuroendocrine malignancy where the role of nuclear medicine imaging is currently limited. This paper investigates the potential diagnostic value of [18F]Fluorocholine PET/CT in primary MTC. METHODS: We prospectively enrolled 25 patients (10 male, 15 female) with suspicion for primary MTC based on fine-needle aspiration biopsy (FNAB). All patients had a baseline three phase [18F]Fluorocholine PET/CT (2.5 MBq/kg): two regional head and neck and upper mediastinum studies at 5 min (first phase) and 120 min (third phase) and a whole-body PET/CT (from the skull vertex to mid-thighs) at 60 min (second phase). Any non-physiological radiotracer uptake was regarded as MTC positive. All patients referred to surgery had a preoperative neck-US. True lesion status was assessed using either histopathology, FNAB results or follow-up imaging and laboratory (calcitonin, CEA) results. Results with p < 0.05 were considered statistically significant. RESULTS: Nineteen of 25 patients (76%) were surgically treated and histopathology reports were obtained. Patient-based sensitivity and positive predictive value for detection of any MTC lesion using [18F]Fluorocholine PET/CT were both 100%. Neck-US was more specific (100% vs 70%; p = 0.002) and had a higher positive predictive value than [18F]Fluorocholine PET/CT (100% vs 55%; p = 0.018) for N1a and N1b staging. [18F]Fluorocholine PET/CT had a higher sensitivity (100% vs 50%; p = 0.025) and higher negative predictive value (100% vs 81%; p = 0.026) than neck-US for N1b staging. The optimal SUVmax cut-off to differentiate malignant from benign neck lesions at 60 and 120 min was 2.56. Patients with M1 stage on PET/CT had higher calcitonin (median of 5,372 vs 496.6 pg/ml; p = 0.005) and CEA concentrations (median of 95.8 vs 18.65 µg/l; p = 0.034) compared to patients with M0 disease. CONCLUSION: [18F]Fluorocholine PET/CT appears to be a promising radiotracer for primary staging of MTC by increasing diagnostic accuracy for N staging and detecting possible distant metastatic sites at initial presentation of disease.

Incidence of thyroid disorders in the second decade of adequate iodine supply in Slovenia.

BACKGROUND: The incidence of thyroid disorders importantly depends on iodine supply and may change over time. There are only a few data available regarding the change in the incidence of thyroid disorders following the increase in iodine supply. Therefore, the aim of this study was to establish the incidence of thyroid disorders in the second decade of adequate iodine supply in Slovenia. METHODS: The medical records of 17,828 adult patients who were examined at this department for the first time in the years 2011, 2012, 2013 and 2014 were reviewed. The incidence of diffuse and nodular goiter, thyroid autonomy, Graves' disease, non-hypothyroid and hypothyroid Hashimoto's thyroiditis in the stable catchment area of the University Medical Centre Ljubljana with 1,000,000 inhabitants was followed. RESULTS: A significantly lower incidence of thyroid autonomy was observed in the year 2014 as compared to 2011 (p = 0.006), a significantly higher incidence of Hashimoto's thyroiditis in 2014 as compared to 2013 (p = 0.003), and a significantly higher incidence of non-hypothyroid Hashimoto's thyroiditis in 2014 as compared to 2011 and 2013 (p = 0.005 and p = 0.022, respectively). The incidence of other thyroid diseases did not change significantly in the observed period. CONCLUSION: In the second decade of adequate iodine supply in Slovenia, we established a similar or even a lower incidence of most thyroid diseases in the observed 4 years with the exception of Hashimoto's thyroiditis.

Nutrihealth Study: Seasonal Variation in Vitamin D Status Among the Slovenian Adult and Elderly Population.

Several studies conducted around the world showed substantial vitamin D insufficiency and deficiency among different population groups. Sources of vitamin D in the human body include ultraviolet B (UVB)-light-induced biosynthesis and dietary intake, but people's diets are often poor in vitamin D. Furthermore, in many regions, sun exposure and the intensity of UVB irradiation during wintertime are not sufficient for vitamin D biosynthesis. In Slovenia, epidemiological data about vitamin D status in the population were investigated through a national Nutrihealth study-an extension to the national dietary survey SI.Menu (2017/18). The study was conducted on a representative sample of 125 adult (18-64 years) and 155 elderly (65-74 years old) subjects, enrolled in the study in different seasons. Their vitamin D status was determined by measuring the serum 25-hydroxy-vitamin D (25(OH)D) concentration. Thresholds for vitamin D deficiency and insufficiency were 25(OH)D levels below 30 and 50 nmol/L, respectively. Altogether, 24.9% of the adults and 23.5% of the elderly were found to be vitamin D deficient, while an insufficient status was found in 58.2% and 62.9%, respectively. A particularly concerning situation was observed during extended wintertime (November-April); vitamin D deficiency was found in 40.8% and 34.6%, and insufficient serum 25(OH)D levels were observed in 81.6% and 78.8%, respectively. The results of the study showed high seasonal variation in serum 25(OH)D levels in both the adult and elderly population, with deficiency being especially pronounced during wintertime. The prevalence of this deficiency in Slovenia is among the highest in Europe and poses a possible public health risk that needs to be addressed with appropriate recommendations and/or policy interventions.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

18F-Fluorocholine PET/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99mTc-sestamibi SPECT/CT, 99mTc-sestamibi/pertechnetate subtraction imaging, and 99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%-56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%-34% (44% combined). Conclusion:18F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

Hypothyroidism is associated with higher testosterone levels in postmenopausal women with Hashimoto's thyroiditis.

INTRODUCTION: There are few data about possible interaction of sex hormones and thyroid autoimmunity and function in women with Hashimoto's thyroiditis (HT) after menopause. Therefore, our aim was to investigate sex hormone levels in euthyroid (EuHT) and hypothyroid (HypoHT) postmenopausal women with HT. MATERIAL AND METHODS: We performed a prospective observational clinical study that included 55 women with HT (AllHT) and 18 healthy subjects (HS) after menopause matched by age, body mass index, follicle-stimulating hormone, and menopause duration. According to their thyrotropin (TSH) level, the AllHT patients were divided into two subgroups: EuHT with TSH in the range 0.35-5.5 mU/L and HypoHT with TSH above 5.5 mU/L. Total and free testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E2), and progesterone (P) were measured in all subjects. Values are presented as mean ± SD. The Mann-Whitney U test was used for comparison of values between the groups. Correlations were tested using Kendall's tau test. RESULTS: In the HypoHT group, significantly higher free T levels were found in comparison to the HS group (7.89 ± 3.55 pmol/L and 7.13 ± 3.03 pmol/L, p < 0.05). Furthermore, in HypoHT, free T was significantly higher than in EuHT (7.19 ± 5.65 pmol/L, p < 0.05). SHBG was significantly lower in HypoHT compared with HS (45.4 ± 17.4 nmol/L and 60.09 ± 19.51 nmol/L, p < 0.05). No significant correlation was found between sex hormone levels and thyroglobulin and thyroid peroxidase antibodies. CONCLUSION: We report significantly higher free and total T levels in hypothyroid postmenopausal women with HT. To our knowledge, this is the first study of sex hormone levels in postmenopausal women with HT.

The effects of image reconstruction algorithms on topographic characteristics, diagnostic performance and clinical correlation of metabolic brain networks in Parkinson's disease.

PURPOSE: The purpose of this study was to evaluate the effects of different image reconstruction algorithms on topographic characteristics and diagnostic performance of the Parkinson's disease related pattern (PDRP). METHODS: FDG-PET brain scans of 20 Parkinson's disease (PD) patients and 20 normal controls (NC) were reconstructed with six different algorithms in order to derive six versions of PDRP. Additional scans of 20 PD, 25 atypical parkinsonism (AP) patients and 20 NC subjects were used for validation. PDRP versions were compared by assessing differences in topographies, individual subject scores and correlations with patient's clinical ratings. Discrimination of PD from NC and AP subjects was evaluated across cohorts. RESULTS: The region weights of the six PDRPs highly correlated (R ≥ 0.991; p < 0.0001). All PDRPs' expressions were significantly elevated in PD relative to NC and AP subjects (p < 0.0001) and correlated with clinical ratings (R ≥ 0.47; p < 0.05). Subject scores of the six PDRPs highly correlated within each of individual healthy and parkinsonian groups (R ≥ 0.972, p < 0.0001) and were consistent across the algorithms when using the same reconstruction methods in PDRP derivation and validation. However, when derivation and validation reconstruction algorithms differed, subject scores were notably lower compared to the reference PDRP, in all subject groups. CONCLUSION: PDRP proves to be highly reproducible across FDG-PET image reconstruction algorithms in topography, ability to differentiate PD from NC and AP subjects and clinical correlation. When calculating PDRP scores in scans that have different reconstruction algorithms and imaging systems from those used for PDRP derivation, a calibration with NC subjects is advisable.