Václav Zamrazil

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

Abstract 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.

The Elimination of Iodine Deficiency in the Czech Republic: The Steps Toward Success

The Czech Republic has a long history of iodine deficiency. Salt iodization was introduced in 1947, followed by a progressive correction of iodine deficiency. The present study reports the changes in the status of iodine nutrition and of thyroid function in the country from 1994 to 2002. The study included 29612 individuals, aged 0 to 98 years, including 5263 individuals randomly selected from the general population and 24349 individuals who attended the Institute of Endocrinology of Prague (hospital population). Urinary iodine was determined in all individuals. Measurements of serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroglobulin (Tg), were taken in 8544 to 19060 individuals. The iodine content of table salt was measured in 1130 samples. The median urinary iodine in the general and hospital populations were not significantly different. They progressively increased with time, starting from values indicating mild iodine deficiency (88-95 microg/L) prior to 1997, reaching the critical threshold of 100 microg/L in 1998, and optimal values between 120-140 microg/L since 2000. There was only a low and not significant positive correlation between the iodine content of salt and the urinary iodine. In contrast, urinary iodine showed marked seasonal changes, with the highest values during winter, when livestock were supplemented by mineral tablets containing iodine. Variables exploring thyroid function were all situated within the normal range in adults but another study (results not reported) has shown the persistence of slightly elevated TSH in neonates. The correction of iodine deficiency was not accompanied by unfavorable side effects. In conclusion, the Czech Republic has achieved sustainable elimination of iodine deficiency. Salt iodization has been a determining, but not the only, factor responsible for the success. Iodine supplementation of livestock and increased consumption of milk rich in iodine have probably played a determining role. Neonatal thyroid screening could constitute the major monitoring tool in order to insure sustainable elimination of iodine deficiency in the Czech Republic.

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

Abstract 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 24h. 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.

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.

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.

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

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.

Thyroglobulin as an Indicator of Iodine Intake

Serum thyroglobulin (Tg) is a good marker of iodine intake and is raised according to the level of iodine insufficiency. According to population studies, thyroglobulin (Tg) as a product of thyroid epithelial cells also seems to be a valuable indicator of thyroid status, due to its sensitivity to recent changes in iodine nutrition. Serum Tg was found to be elevated in iodine-deficient areas. In addition, the prevalence of autoantibodies against Tg in more than 10% of healthy individuals is an important limitation concerning both the precision and the accuracy of immunoanalytically measured serum Tg, mainly if immunometric techniques are used. Tg reflects three factors: the mass of differentiated thyroid tissue present, any physical damage to or inflammation of the thyroid gland and the magnitude of TSH receptor stimulation. Thyroid volume, thyroid nodularity, or iodine excretion have close associations to serum Tg, one of the largest iodoglycoproteins in the body with a complex three-dimensional structure, which originates only in the thyroid gland. It can be concluded that Tg is a valuable indicator of iodine nutrition in a population, if thyroid disorders are infrequent. However, precision, reproducibility, and accuracy of immunoanalytical kits must be improved to obtain comparable results among various laboratories.

Dysthyronemia in normal concentrations of thyrotropin – analytical and clinical consequences

Abstract 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.

Abstract 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.

Evaluation of Iodine Prophylaxis in the Czech Republic: Changes in Ioduria, Thyroid Status and Autoimmunity

This chapter evaluates the effects of iodine prophylaxis programs on ioduria, thyroid function and thyroid volume, and the presence of antibodies against thyroglobulin and thyroid peroxidase. Examinations were done for a randomly chosen sample of population from three regions of the Czech Republic, using the same methodology at 5-year intervals. Examination of 3587 individuals of both genders aged 6–65 years was done. The results showed no homogenous rise in ioduria, with a decline in lower values and an increase in high values—especially in children. There was no change in the distribution of TSH values, but there was a significant decline in low values of FT4 and a rise in normal values. Thyroid volume did not change among men, but the number of women with enlarged thyroid volumes decreased. A disturbing trend was proved for thyroid antibodies: in women there was a statistically significant rise in the occurrence of high levels of thyroglobulin and thyroid peroxidase antibodies; while in men, only the changes in antibodies against thyroid peroxidase were significant. Although effectivity and positive consequences of improved iodine supplementation in our study prevails, it seems be necessary to systematically monitor quality of the program and also its possible unfavorable effects in the future.