[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.

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.

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.

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.

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 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.

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.

Ten-year follow-up of thyroid epidemiology in Slovenia after increase in salt iodization.

AIM: To assess iodine supply and follow thyroid epidemiology for ten years after an iodine increase from 10 to 25 mg of potassium iodide per kilogram of salt in 1999. METHODS: In 2002 and 2003, we determined the thyroid size by palpation and ultrasound and measured urinary iodine concentration (UIC) in 676 schoolchildren from 34 schools throughout Slovenia. From 1999 to 2009, we followed the incidence of diffuse and nodular goiter, thyroid autonomy, Graves' disease, and Hashimoto's thyroiditis among adults in the stable catchment area of the University Medical Centre Ljubljana with 1000000 inhabitants. RESULTS.:In children, only 1% had a goiter grade 2 (visible and palpable thyroid gland), median thyroid volume was 5.8 mL, and median UIC was 148 µg/L. In adults, the incidence of diffuse goiter and thyroid autonomy decreased significantly (2009 vs 1999, rate ratio [RR], 0.16; 95% confidence interval [CI], 0.12-0.21 and RR, 0.73; 95% CI, 0.62-0.86, respectively), with a lower incidence in younger participants in 2009 (P<0.001). The incidence of multinodular goiter and solitary nodule increased (2009 vs 1999, RR, 1.55; 95% CI, 1.35-1.79 and RR, 1.72; 95% CI, 1.49-1.99, respectively). No long-term changes were observed for Graves' disease (2009 vs 1999, RR, 0.95; 95% CI, 0.81-1.13), while the incidence of Hashimoto's thyroiditis increased strongly (2009 vs 1999, RR, 1.86; 95% CI, 1.64-2.12). CONCLUSIONS: The change from mildly deficient to sufficient iodine supply was associated with a marked change in the incidence of thyroid epidemiology - a significant decline in the incidence of diffuse goiter and thyroid autonomy and a marked increase in the incidence of Hashimoto's thyroiditis.

The outcome of 131I treatment in Graves' patients pretreated or not with methimazole.

Despite extensive use of iodine-131 ((131)I) treatment for Graves' hyperthyroidism, the optimal regimen of pretreatment with antithyroid drugs is still a matter of discussion. Our aim was to evaluate the success of (131)I treatment in patients with Graves' disease without and with pretreatment with methimazole (MMI). In a prospective randomized study 156 patients with Graves' disease were treated with fixed activity of 550 MBq (131)I. First group of 59 patients received only (131)I. The second group of 50 patients received MMI which was stopped seven days before (131)I. The third group of 47 patients received MMI until (131)I application. Patients were followed clinically and biochemically 1, 3, 6 and 12 months after (131)I treatment. Absorbed dose of (131)I and thyroid volume were measured in each patient. Our result showed that (131)I treatment success after twelve months was equally effective in the first and second group (96.6% and 96%, respectively), while in the third group, success was significantly lower (63.8%). Accordingly, the absorbed dose of (131)I was significantly higher in the first and in second group (144±104 Gy and 164±107 Gy, respectively), and lower in the third group (105±58 Gy). Thyroid volume gradually decreased without any significant difference between the three groups. In conclusion, our study provides evidence that application of (131)I is equally effective in the nonpretreated with MMI group and in the group discontinuing MMI one week before (131)I treatment, and it is more effective in these two groups as compared to the group in which pretreatment with MMI was administered till the day of (131)I application.

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.

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.