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.

[Thyroid disease in the Czech Republic: the EUthyroid project and the evaluation of the General Health Insurance Company epidemiological data for the period of 2012-2015]. / Onemocnení stítné zlázy v Ceské republice: projekt EUthyroid a vyhodnocení epidemiologických dat VZP za období let 2012-2015.

Institute of Endocrinology participates in the grant of European Commission EUthyroid (Towards the elimination of iodine deficiency and preventable thyroid-related diseases in Europe), together with other 28 European countries. The role of Institute of Endocrinology in EUthyroid is among other things to ensure access to national registers relating to thyroid diseases. The results presented here correspond to the years 2012-2015 and are based on data from the General Health Insurance Company Czech Republic (VZP CR), which has 6 million insured persons (ratio male : female = 1 : 1). The set is sufficiently representative to be related to the whole of the Czech Republic. According to VZP data, the prevalence of thyreopathies is constantly increasing, for example according to the code of diagnoses E00-E07 and the unique birth number, the prevalence of thyreopathies increased from 6.8 % in 2012 to 7.5 % in 2015. The increase of the prevalence is mainly concentrated to clinical manifestation of hypothyroidism (code E03, an increase from 2.8 % in 2012 to 3.2 % in 2015); the second is nontoxic struma (code E04), which had a constant prevalence of 2.5 % in the given period. On the other hand, thyroiditis (code E06), the third in the order of occurrence, increased from 1.8 % in 2012 to 2 % in 2015. The decrease in prevalence only occurred in hyperthyroidism (E05) from 0.7 % in 2012 to 0.6 % in 2015. Other thyreopathies had a prevalence of less than 1 %, and was constant between 2012 and 2015 (other thyroid disorders E07 0.8 %, thyroid disorders associated with iodine deficiency E01 0.2 %, E02 0.07 %, E00 0.01 %, thyroid carcinoma C73 0.13 %).Key words: EUthyroid - General Health Insurance Company- occurrence of thyreopathies - thyroid disease in the Czech Republic.

[Iodine supply of pregnant women in the Czech Republic]. / Zásobení jodem u tehotných zen v Ceské republice.

INTRODUCTION: Iodine deficiency is a global public health problem which is particularly noticeable in pregnant or breastfeeding women and their children. Even mild iodine deficiency during pregnancy can lead to damage to the developing brain and thus affecting the fetus intelligence, his cognitive and neurological function, embryogenesis and growth. PATIENTS: In the period 2010-2015 was determined by spectrophotometry at the Institute of Endocrinology the basal urinary iodine in 532 pregnant women at the age of 32 ± 5 (18-44) years, which came from Prague, Hradec Kralove and Mlada Boleslav. It was located 349 women in the first trimester, 112 in the second trimester, and 71 women in the third trimester. In the monitoring of pregnant women in the first trimester 218 basal urine samples of women were determined by mass spectrometry with inductively coupled plasma (ICP MS) in The National Institute of Public Health (NIPH). Women came from the 6 areas in the Czech Republic. Development of urinary iodine in the general population in the period 1994-2015 was observed in patients who underwent Institute of Endocrinology and from population studies conducted in 7 regions of the Czech Republic. It performed 52 648 spectrophotometric analysis of urinary iodine in the general population. METHODS: Urinary iodine was determined by alkali melting of urine samples, followed by spectrophotometric determination of iodine in the form of iodide using the Sandell-Kolthoff reaction in the Institute of Endocrinology or determination was performed by ICP-MS in the laboratory of NIPH. RESULTS: On average, only 21.8 % of pregnant women had urinary iodine values determined by spectrophotometry higher than 150 µg/L. The results of iodine nutrition of pregnant women in the first trimester analyzed using ICP-MS are better, but even so, only 50.5 % of pregnant women have urinary iodine higher than 150 µg/L. CONCLUSION: The results of iodine nutrition of pregnant women are alarming, on average, only 30 % of the total of 750 examined women have urinary iodine values greater than 150 µg/L and therefore meet the requirements of the WHO for pregnant women. Our results, however, show that iodine deficiency is not major public health problem in the general population.Key words: ICP-MS - pregnant women - Sandell-Kolthoff reaction - urinary iodine.

[Urinary iodine concentration in adult patients with type 1 diabetes mellitus]. / Jodurie u nemocných s diabetes mellitus 1. typu Vztahy k vybraným parametrum charakterizujícím diabetický syndrom.

INTRODUCTION: In patients with type 1 and 2 diabetes mellitus only rare data concerning the status of iodine supplementation and impact of possible iodine deficiency is available. AIM: To get basic information about (a) state of supply with iodine in patients with type 1 diabetes mellitus (DM1T), (b) the difference from non-diabetic population, (c) possible association of iodine saturation with some clinical and laboratory features of the diabetic syndrome, including the state of thyroid gland. SUBJECTS AND METHODS: We examined 54 men and 51 women treated with DM1T in a cross-sectional study. Age: median 42 years (25th quartil 31, 75th quartil 55), DM1T duration: 18 years (13, 23), BMI: 25.9 (23.3, 29.7), HbA1c: 61 mmol/mol (51, 71), creatinine: 71 µmol/l (61, 83), micro-albuminuria 4.3 µg/min (1.9, 11.8), TSH: 1.77 mIU/l (1.12, 2.80). The iodine saturation was evaluated using iodine concentration in a sample of first morning urine. RESULTS: Urinary iodine concentration in the whole group: median 152 µg/l, 25th quartile 117 µg/l, 75th quartile 219 µg/l. More than 50 % of the urinary iodine samples fell within range of optimal saturation (100-200 µg/l), 13 % within insufficient saturation (< 100 µg/l), 35 % of the samples showed increased saturation (> 200 µg/l), in which 2/3 were men. Using multiple regression analysis we found significant positive association of urinary iodine concentration and male gender, body weight, stature, and serum creatinine. No relation between urinary iodine and clinical and laboratory features of the diabetic syndrome was found. CONCLUSIONS: Iodine saturation in examined patients with DM1T was in accordance with ICCIDD (WHO) requirements for optimal/good saturation in non-diabetic population. With respect to the chosen normal urinary iodine concentration, eg. 100, resp. 150 µg/l the features of diabetic syndrome were not different. The question whether other factors than general measures taken in the past for solution of the iodine deficiency in the Czech Republic are involved in good level of iodine saturation in patients with DM1T should be addressed in further investigations comprising larger cohorts of patients.Key words: diabetes mellitus - urinary iodine concentration.

Ensuring Effective Prevention of Iodine Deficiency Disorders.

BACKGROUND: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention. SUMMARY: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. CONCLUSION: Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.

[Subclinical thyroid disease]. / Subklinické tyreopatie.

Importance of subclinical thyroid disease (STh) is now a matter of discussion. Definition of this unit is laboratory: in presence of normal level of thyroxine (T4) TSH value is changed: in lower TSH level the subclinical hyperthyroidism (STx) in increase TSH levels subclinical hypothyroidism (SH) is present. Risk of clinical manifestation is two three times highter in comparison with persons with normal TSH level. Clinical importance STh is still not evaluated definitively. SH caused disturbance of lipid metabolism, elasticity of vessels and endothelial function and therefore increases risk of atherosclerosis. STx causes electrical instability of myocardium with increased risk of arythmias, increases risk of osteoporosis and other changes. Most important are effects of STh in cardiology, reproductive medicine and gynecology. Clinical significance of these effects is not definitively evaluated.

The significance of plasma adrenomedullin and calcitonin gene-related peptide concentration in patients with Type 2 diabetes mellitus who are treated for cardiovascular risk factors.

OBJECTIVES: To evaluate the significance of plasma adrenomedullin and calcitonin gene-related peptide (CGRP) concentration in patients with Type 2 diabetes mellitus who are treated for hypertension and dyslipidemia. METHOD: Plasma adrenomedullin and CGRP concentration, transthoracal echocardiography and ABPM were evaluated in 82 patients with Type 2 diabetes mellitus and 41 control subjects with no previous cardiovascular disease. All the subjects had casual blood pressure ≤140/90 mmHg or received antihypertensive medication, were treated by statin if LDL cholesterol was≥3mmol/L, by fibrates if triacylglyceroles≥2 mmol/L. RESULTS: The mean age was 61±6 in patients with diabetes mellitus and 61±5 years in control subjects (p=0.9). Plasma CGRP was 3.0±1.8 in patients with diabetes mellitus and 2.3±1.0 ng/ml in control subjects (p=0.09). Plasma adrenomedullin was 2.2±0.9 in patients with diabetes mellitus and 2.8±1.1 ng/ml in control subjects (p=0.01). In patients with diabetes mellitus mass index of the left ventricle was significantly higher and the parameters of diastolic function were more deteriorated. Plasma adrenomedullin and CGRP correlated significantly negatively with serum creatinine and positively with mean 24 hours arterial blood pressure in patients with diabetes mellitus but not in control subjects. Plasma adrenomedullin concentration in patients with diabetes mellitus treated for hypertension was significantly reduced. CONCLUSION: Despite concentration plasma adrenomedullin and CGRP modulation by cardioprotective treatment both neuropeptides remained involved in regulation of hemodynamic and metabolic parameters in patients with Type 2 diabetes mellitus. The low plasma of adrenomedullin in patients with Type 2 diabetic may be marker of the efficient intervention on cardiovascular risk factors.

Mild iodine deficiency in women after spontaneous abortions living in an iodine-sufficient area of Czech Republic: prevalence and impact on reproductive health.

OBJECTIVE: Iodine deficiency is associated with thyroid dysfunction and adverse pregnancy outcomes. The aim of our study was to investigate the status of iodine saturation in women after spontaneous abortion (SpA) residing in an iodine-sufficient area and to evaluate their subsequent reproductive health. DESIGN: Nonrandomized prospective follow-up study. PATIENTS AND METHODS: We compared urinary iodine concentration (UIC) in 171 women 2-8 weeks (median 4) after an early SpA with age-matched controls. Women with known thyroid diseases were excluded. We also analysed a relationship of UIC to serum thyroid-stimulating hormone, free thyroxine, antibodies against thyroid peroxidase and thyroid ultrasound. Afterwards, we followed the women for a median of 38 months (range 12-47). We used a multivariate regression analysis to assess the influence of iodine status and other thyroid biochemical and ultrasound parameters on their subsequent reproductive health. RESULTS: Women after SpA were almost twice as likely to suffer from mild iodine deficiency and had lower median UIC as compared to age-matched controls [rate 105/181 (58·0%) vs 57/181 (31·5%), P < 0·001, medians UIC 92·00 vs 117·80 mcg/l, P < 0·001]. UIC was not influenced by the use of iodine supplements in the previous pregnancy. We did not find any association neither between UIC and thyroid dysfunction and/or thyroid antibodies, nor between UIC and rates of subsequent successful pregnancies or obstetric complications. CONCLUSIONS: More than half of women after SpA residing in an iodine-sufficient area are suffering from mild iodine deficiency. However, it does not seem to have a negative impact on their subsequent reproductive health.

Dysthyronemia in normal concentrations of thyrotropin--analytical and clinical consequences.

This article discusses the conditions that may lead to a phenomenon called dysthyronemia. Here, the thyroid gland has concentration of thyrotropin in circulation within the reference range, but the concentrations of free or total fractions of thyroid hormones are outside the reference range. Normal values of thyrotropin (TSH) and increased values of THs are referred to as hyperthyroxinemia, while normal values of thyrotropin and decreased values of thyroid hormone are hypothyroxinemia. As shown by our observations, it is a relatively frequent situation in the parallel determinations of TSH and free thyroxine, when results verging on hyperthyroxinemia were found in 7% of cases (6.74%, n=259,590), and also in the parallel sets of TSH and total triiodothyronine when hypotriiodothyroninemia reached 8.5% (8.48%, n=73,143). We are assuming that the main cause of hyperthyroxinemia in the free thyroxine and TSH system is the presence of autoantibodies against thyroxine in patients with autoimmune thyroid disease. The reason of hypotriiodothyroninemia in the system of triiodothyronine and TSH is a decreased concentration of thyroid binding globulin in postmenopausal women. Manufacturers of immunoanalytical kits should take into account the potential adverse effects of autoantibodies against thyroid hormones when measuring the results of immunoassay determination of the free fraction of these hormones.

Evaluation of dysthyronemia in endocrinological patients.

BACKGROUND: Dysthyronemia is the state of the thyroid gland in which the concentration of thyrotropin (TSH) in circulation is within the reference range, but the concentrations of free or total fractions of thyroid hormones (TH) are outside the reference range. Normal values of TSH and increased values of TH are referred to as hyperthyroxinemia or hypertriiodothyroninemia, while normal values of TSH and decreased values of TH are called hypothyroxinemia or hypotriiodothyroninemia. METHODS: Thyroid diagnostic tests were carried out at the Institute of Endocrinology, Prague, Czech Republic, in 1999-2009 using the immunoanalytical systems of Roche Diagnostics GmbH, Germany (Elecsys 2010, Modular E170). RESULTS: Hyperthyroxinemia was found in 6.74% of all parallel sets of TSH and free thyroxine (FT4, n=259,590) values. Hypotriiodothyroninemia was observed in 8.48% of all parallel sets of TSH and total triiodothyronine (TT3, n=73,143). The occurrence of hyperthyroxinemia (TSH-FT4) and hypotriiodothyroninemia (TSH-TT3) was >3 times higher than the occurrence of dysthyronemia for the combinations TSH-FT4 (hypothyroxinemia), TSH-TT4 (total thyroxine, n=1996), TSH-FT3 (free triiodothyronine, n=94,090), and TSH-TT3 (hypertrijodthyroninemia), and >5 times higher in comparison with the combinations TSH-FT4-FT3 (n=93,683), TSH-FT4-TT3 (n=72,373), TSH-FT3-TT3 (n=2466), TSH-TT4-TT3 (n=1779), TSH-FT4-TT4 (n=1571), and TSH-FT3-TT4 (n=1466). CONCLUSION: In light of our patient types, we are assuming that the observed hypotriiodothyroninemia (TSH-TT3, 8.48%) is due to a decreased concentration of thyroid binding globulin in postmenopausal women and that hyperthyroxinemia (TSH-FT4, 6.74%) is caused mainly by endogenous autoantibodies against thyroxine in patients with thyroid autoimmune diseases.

The association of masked hypertension in treated type 2 diabetic patients with carotid artery IMT.

OBJECTIVES: To evaluate the association of masked hypertension (MH) in treated type 2 diabetic patients without history of cardiovascular disease with carotid artery target organ damage. METHODS: Sixty-four type 2 diabetic patients treated for hypertension with office BP below 140/90 mm Hg were examined by 24-h BP monitoring and carotid sonography. MH was diagnosed if daily mean ambulatory BP was >or=135/85 mm Hg. The association of MH with carotid artery parameters was evaluated. RESULTS: The average age of patients was 62+/-5 years. Twenty-four patients had MH (37.5%). Carotid artery IMT was 0.74+/-0.08 mm in patients with MH and 0.69+/-0.06 mm without MH (p=0.03). The distensibility of common carotid artery was 0.24+/-0.07 mmHg(-1) in patients with MH and 0.29+/-0.1mm Hg(-1) without MH (p=0.14). After adjustment for age, gender, smoking, duration of diabetes, BMI and clinic blood pressure (BP) values the association of MH with carotid artery IMT was sustained. CONCLUSION: Masked hypertension in treated type 2 diabetic patients is associated with carotid artery IMT.

Adrenocortical function in young adults with diabetes mellitus type 1.

In 75 young adults with diabetes mellitus type 1 (DM 1) we have performed a cross-sectional study to gain more information about their adrenocortical function. We have found in a surprisingly large portion of patients (25%) a subnormal response (<500 nmol/L, low responders) of the serum cortisol during low-dose Synacthen test, accompanied by significantly decreased stimulated values of aldosterone and salivary cortisol. Basal serum cortisol, aldosterone, and dehydroepiandrosterone sulphate (in women only) were significantly reduced in low responders as well, while ACTH, cortisol binding globulin, plasma renin activity, urinary free cortisol/24h, and salivary cortisol did not differ. The results indicate that the disorder of adrenocortical function in low responders occurs in all adrenocortical zones. The patients with the highest risk in respect to revealed hypocorticalism were DM 1 with autoimmune thyroiditis, 13 out of 36 in contrast to 5 out of 39 suffered from isolated form of DM 1, with onset around 30 years, independently on sex. The biorhythm of salivary cortisol in low responders under real-life conditions did not significantly differ from normal responders, except of the decreased values in the morning. Antibodies against 21-hydroxylase and adrenal cortex were negative in the entire group of diabetics studied. In conclusion, this is the first study to demonstrate in as much as 25% of young adults with DM 1 patients without any signs of adrenal autoimmunity decreased both basal and stimulated serum cortisol and aldosterone levels, implying existence of subclinical primary hypocorticalism.

Autoimmune thyroiditis and Helicobacter pylori--is there a connection?

OBJECTIVES: In this study we examined the anti-Helicobacter pylori (anti-H. pylori) antibodies in patients with autoimmune thyroiditis, with and without different polyglandular involvement, and in healthy controls. MATERIAL & METHODS: Patients with autoimmune thyroiditis (AT) were divided into three groups: Group A: 23 patients with isolated AT, Group B: 30 patients with AT as a part of polyglandular activation of autoimmunity, and Group C: 7 patients with AT as a part of autoimmune polyglandular syndrome type II. Thirty healthy individuals served as controls (Group D). Anti-H. pylori antibodies were determined first by ELISA for classes IgG, IgA, and IgM, and subsequently by immunoblot for classes IgG and IgA. RESULTS: ELISA: The number of patients with IgA antibodies in Group A (39%) and Group B (30%) differed significantly from controls (7%, p<0.05). Immunoblot: Anti-CagA antibodies were found in 13% of patients in Group A, 7% of Group B, 0% of Group C, and 20% of Group D. A higher seroprevalence, as compared to controls, was found for IgG to the VacA (p=0.01), 30 kDa (p=0.001), and 17 kDa (p=0.008) antigens in Group A and for IgG to the 30 kDa antigen in Group C (p=0.037). A significantly higher seroprevalence, as compared to controls, was likewise found for IgA to the 17 kDa antigen in Group A (p=0.015). CONCLUSIONS: A different distribution of antibodies to H. pylori antigens was found in patients with isolated AT compared to patients with AT coupled with a polyglandular syndrome.

Actual levels of soy phytoestrogens in children correlate with thyroid laboratory parameters.

Thyroid hormones and thyroid autoantibodies, along with serum concentrations of two phytoestrogens of the isoflavone series, daidzein and genistein, were measured in 268 children without overt thyroid diseases, screened for iodine deficiency in one region of the Czech Republic. Since both phytoestrogens have been reported to inhibit thyroid hormone biosynthesis and in high concentrations to exert goitrogenic effects, we investigated whether their presence in the circulation could influence thyroid hormone function in a population where soy consumption is not common. Correlation analysis revealed a significant positive association of genistein with thyroglobulin autoantibodies and a negative correlation with thyroid volume. Multiple regression analysis of the relationships between actual phytoestrogen levels and measured thyroid parameters revealed only a weak but significant association between genistein and thyroid variables. Higher levels of free thyroxine were found in a subgroup of 36 children who ate soy food in the previous 24 h. In conclusion, only modest association was found between actual phytoestrogen levels and parameters of thyroid function. On the other hand, even small differences in soy phytoestrogen intake may influence thyroid function, which could be important when iodine intake is insufficient.

Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

Spectrophotometric determination of urinary iodine by the Sandell-Kolthoff reaction subsequent to dry alkaline ashing. Results from the Czech Republic in the period 1994-2002.

The Czech Republic is an iodine-deficient area. Insufficient iodine intake was reduced by enriching cooking salt with iodine in the range 20-34 mg I/kg. An important indicator for tracking changes in iodine nutrition over time is accurate information about urinary iodine concentrations in the population. In this paper we describe and characterize our method used for the determination of iodine in biological material, which is based on alkaline ashing of urine specimens preceding Sandell-Kolthoff reaction using brucine as a colorimetric marker. The losses of radioiodine added during sample preparation have not exceeded 0.001%. The detection limit is 2.6 microg I/L and the limit of quantification is 11.7 microg I/L, with intra-assay precision of 4% and inter-assay precision of 4.9%. During the period 1994-2002, the urinary iodine concentration was determined in 29,612 samples in the Institute of Endocrinology. The mean basal urinary iodine concentrations+/-SD were 115+/-69 microg I/L. Of the samples, 0.7% were in severe (<20 microg I/L), 9.6% in moderate (20-49 microg I/L), 40.1% in mild (50-99 microg I/L), 35.6% in adequate (100-200 microg I/L), and 14.0% in more than adequate (>200 microg I/L) subsets of iodine nutrition. A statistically significant (p<0.00001) difference was found between mean male (127 microg I/L) and female (112 microg I/L) urinary iodine, and an inversely proportional trend also exists in the age-related data.