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.

Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension.

A simple graphical quantitative analysis of ultrasonography images to decide when to perform fine needle aspiration biopsy in diagnosing malignancy in solid thyroid nodules? A two centres prospective study.

OBJECTIVE: Since the prevalence of thyroid nodules is high and ultrasonography (USG)-guided fine-needle aspiration biopsy (FNAB) as a diagnostic means cannot be performed in all cases, we aimed to evaluate the feasibility and applicability of simple graphical analysis of USG two-dimensional images, to identify patients with suspicious thyroid nodules who would benefit from FNAB. SUBJECTS AND METHODS: We studied prospectively 211 consecutive patients with thyroid nodules: 122 from the University Clinical Centre (UCC) of Maribor and 89 from the University Medical Centre (UMC) of Ljubljana who underwent USGguided FNAB from January 2011 to October 2013. The cytology report was categorized as benign or suspicious/malignant. Blind to cytology reports, we later performed graphical analysis of USG images using ImageJ (version 1.48r) which is a public domain Java image processing and analysis programme. We compared the average gray value and standard deviation (SD) of the gray values used to generate the mean gray within the selection, with cytology reports. RESULTS: According to cytology reports, 24 thyroid nodules were suspicious/malignant (14/10) and 187 benign. Graphical analysis of USG images performed with ImageJ demonstrated significantly higher values of SD of the gray values used to generate the mean gray value in suspicious/malignant thyroid nodules as compared to unsuspicious nodules in both UCC Maribor and in UMC Ljubljana (P<0.001 and P=0.002, respectively). A higher value of the SD of gray value used to generate the mean gray value meant variation or dispersion from the average value and was correlated by the presence of micro-calcifications. By applying a cut-off level of the quotient between the SD value of an examined thyroid nodule and the SD value of normal/reference thyroid tissue of 1.20, we found that 21/24 nodules were classified as true positive and 114/187 as true negative. CONCLUSION: Our results showed that our graphical quantitative analysis of USG images had a negative predictive value of more than 90% and was able to suggest which thyroid nodules were potentially malignant and needed further investigation.

Thyroid lesions incidentally detected by (18)F-FDG PET-CT - a two centre retrospective study.

BACKGROUND: Incidental (18)F-FDG uptake in the thyroid on PET-CT examinations represents a diagnostic challenge. The maximal standardized uptake value (SUVmax) is one possible parameter that can help in distinguishing between benign and malignant thyroid PET lesions. PATIENTS AND METHODS: We retrospectively evaluated (18)F-FDG PET-CT examinations of 5,911 patients performed at two different medical centres from 2010 to 2011. If pathologically increased activity was accidentally detected in the thyroid, the SUVmax of the thyroid lesion was calculated. Patients with incidental (18)F-FDG uptake in the thyroid were instructed to visit a thyroidologist, who performed further investigation including fine needle aspiration cytology (FNAC) if needed. Lesions deemed suspicious after FNAC were referred for surgery. RESULTS: Incidental (18)F-FDG uptake in the thyroid was found in 3.89% - in 230 out of 5,911 patients investigated on PET-CT. Malignant thyroid lesions (represented with focal thyroid uptake) were detected in 10 of 66 patients (in 15.2%). In the first medical centre the SUVmax of 36 benign lesions was 5.6 ± 2.8 compared to 15.8 ± 9.2 of 5 malignant lesions (p < 0.001). In the second centre the SUVmax of 20 benign lesions was 3.7 ± 2.2 compared to 5.1 ± 2.3 of 5 malignant lesions (p = 0.217). All 29 further investigated diffuse thyroid lesions were benign. CONCLUSIONS: Incidental (18)F-FDG uptake in the thyroid was found in 3.89% of patients who had a PET-CT examination. Only focal thyroid uptake represented a malignant lesion in our study - in 15.2% of all focal thyroid lesions. SUVmax should only serve as one of several parameters that alert the clinician on the possibility of thyroid malignancy.

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.

Patients with Central Hypothyroidism are Less Sufficiently Treated with Levothyroxine than Patients with Primary Hypothyroidism.

BACKGROUND: Contrary to patients with hypothyroidism after radioiodine (HRI) or after thyroidectomy (HTh), patients with central hypothyroidism (CH) cannot rely on thyrotropin (TSH) level to guide their treatment with L-thyroxine (L-T4). Consequently, they are at constant risk of under- or overtreatment. We aimed to establish the adequacy of L-T4 treatment in patients with CH in our cohort. METHODS: Consecutive patients with CH on L-T4 treatment were compared with patients adequately treated for HRI or HTh. Levels of free thyroxine (fT4) and free triiodothyronine (fT3) were evaluated and the fT4/fT3 ratio was calculated. RESULTS: Forty patients with CH, 136 patients with HRI and 43 patients with HTh were included in this study. Patients with HRI were significantly younger than patients with HTh and CH (p<0.001 for both). Levels of fT4 were significantly lower in CH than in adequately treated patients with HRI and HTh (median (range), 15.6 (12.7-21.3), 18.4 (12.2-28.8), and 18.7 (13.8-25.5) pmol/L, respectively, p<0.001 for both comparisons). Levels of fT3 did not differ significantly (p=0.521) between CH, HRI and HTh (median (range), 4.5 (2.7-5.9), 4.3 (3.2-6.2), and 4.4 (2.9-5.5) pmol/L, respectively). Accordingly, the fT4/fT3 ratio was significantly lower in the CH group than in HRI and HTh groups (median (range), 3.7 (2.5-5.2), 4.2 (1.2-7.7), and 4.4 (2.5-6.1), respectively, p<0.001 for both comparisons). CONCLUSIONS: Patients with CH have lower fT4 levels and lower fT4/fT3 ratios than patients adequately treated for HRI or HTh. The cause for this difference may be the unreliable TSH levels in patients with CH.

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.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

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.

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.

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.

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.

Effects of Adequate Iodine Supply on the Incidence of Iodine-Induced Thyroid Disorders in Slovenia.

BACKGROUND: This study aimed to establish the changes in the incidence and characteristics of iodine-induced hyperthyroidism (II-Hyper) and iodine-induced hypothyroidism (II-Hypo) in the two-year period before and the 10-year period after the increase in mandatory salt iodization from the previous 10 mg/kg of potassium iodide to 25 mg/kg in 1999. Furthermore, the aim was to determine the duration of treatment in II-Hyper patients, since no data regarding severity and treatment of II-Hyper with respect to iodine supply are available. METHODS: This retrospective study reviewed medical records of 885 Slovenian patients first diagnosed with II-Hyper or II-Hypo between 1998 and 2009 at the Thyroid Department of the University Medical Centre Ljubljana. II-Hyper and II-Hypo were diagnosed by one out of 10 senior internal medicine specialists. The diagnosis was based on an adequate patient history, and laboratory measurements of thyrotropin, thyroid hormones, and thyroid antibodies. In most cases, thyroid ultrasound and thyroid scintigraphy were performed. Demographic characteristics and the type and the duration of treatment were also reviewed. RESULTS: The incidence of II-Hypo was significantly higher after the increase in iodine supply than it was before (p < 0.001). After the increase in iodine supply, the incidence of II-Hyper was significantly lower than before the increase (p < 0.001). Furthermore, the portion of patients with overt hyperthyroidism decreased, predominantly due to the increased proportion of patients with subclinical hyperthyroidism (p = 0.007 and p = 0.015, respectively). The duration of treatment with antithyroid drugs and perchlorate was significantly shorter after the increase in iodine supply than it was before (p = 0.001 and p = 0.002, respectively). A significantly positive correlation between the year of the occurrence of excessive iodine intake (EII)-induced thyroid disease and the duration of treatment with amiodarone was found (R = 0.132; p = 0.048), suggesting that the longer the patients had an adequate iodine supply, the longer they could take amiodarone before EII-induced thyroid disorder developed. CONCLUSIONS: After the increase in iodine supply, a higher incidence of II-Hypo and a lower incidence of II-Hyper were observed than before the increase. Less severe II-Hyper, shorter duration of treatment of II-Hyper, as well as a longer thyroid disease-free period in patients on amiodarone are additional beneficial clinical consequences after the establishment of an adequate iodine supply.

Epidemiological trends of iodine-related thyroid disorders: an example from Slovenia.

The epidemiology of thyroid disorders is significantly associated with iodine supply. In 1999, Slovenia increased iodine content in kitchen salt from 10 mg to 25 mg of potassium iodide per kg of salt. According to the WHO criteria, Slovenia shifted from a mildly iodine-deficient country to a country with adequate iodine intake. Ten years after the increase in iodine intake, the incidence of diffuse goitre and thyroid autonomy decreased. Now patients with diffuse goitre and thyroid autonomy reach older age than the patients before the increase in iodine intake. In addition, patients with thyroid autonomy are less frequently hyperthyroid than ten years ago and iodine-induced hyperthyroidism is less severe. The incidence of highly malignant thyroid carcinoma has also dropped. However, the incidence of Hashimoto's thyroiditis increased, most probably in genetically predisposed individuals. Over the last ten years, many animal and in vitro studies evaluated the effects of endocrine disrupting chemicals (EDC) on various aspects of the thyroid function. They mostly studied the effects of polychlorinated biphenyls (PCBs) and dioxins, brominated flame retardants, phthalates, bisphenol A, perfluorinated chemicals, and perchlorate. However, human studies on the effects of EDCs on the thyroid function are very scarce, especially the long-term ones. What they do suggest is that PCBs and dioxins interfere with the transport of thyroid hormones and adversely affect the thyroid function. Many authors agree that iodine deficiency predisposes the thyroid gland to harmful effects of EDCs. Therefore the effects of EDCs in iodine-deficient areas could be more severe than in areas with adequate iodine intake.

Skin microvascular reactivity in patients with hypothyroidism.

Hypothyroidism is associated with impaired vascular function; however, little is known about its impact on microcirculation. We aimed to determine skin microvascular reactivity in hypothyroidism focusing on endothelial function and the sympathetic response. We measured skin laser Doppler (LD) flux (LDF) on the volar forearm and the finger pulp using LD flowmetry in hypothyroid patients (N = 13) and healthy controls (N = 15). Skin microvascular reactivity was assessed by a three-minute occlusion of the brachial artery, inducing postocclusive reactive hyperaemia (PRH), and by a four-minute local cooling of the hand. An electrocardiogram (ECG), digital artery blood pressure and skin temperature at the measuring sites were recorded. Baseline LDF, the digital artery blood pressure and the heart rate were comparable between patients and controls. On the other hand, patients exhibited significantly longer PRH duration, significantly higher blood pressure during cooling (unpaired t-test, p <0.05) and lower, albeit not significant, LDF in the ipsilateral finger pulp during cooling compared to controls. Unexpectedly, the results of the present study point to an increased vasodilator capacity of skin microcirculation and an apparent increase in sympathetic reactivity after local cooling in hypothyroid patients. Hypothyroidism induces subtle changes of some haemodynamic parameters in skin microcirculation implying altered endothelial function and altered sympathetic reactivity.