Metabolic profile and sex hormone binding globulin (SHBG) in different reproductive phases of Czech women and their relations to weight, body composition and fat distribution.

In our study, 213 healthy Czech women aged 20 to 65 years were examined and divided into fully reproductive, premenopausal, menopausal and postmenopausal groups. In all subjects body composition was determined by classical anthropometry and metabolic profile was assessed. A total of 146 subjects completed 3-year longitudinal study. Total and LDL cholesterol increased and ratio HDL/total cholesterol decreased with age (p<0.001), most significantly in menopause. Triacylglycerols increased only up to menopause. HDL had a very slight trend to decrease in menopause and postmenopause. Fasting blood glucose level increased progressively (p<0.001), in postmenopause frequently exceeded normal range. Higher BMI, total fat mass and central fat indices were associated with higher total and LDL cholesterol, triacylglycerols, C-peptide, insulin and fasting blood glucose level (p<0.001; fasting blood glucose level to waist-to-hip ratio: p<0.01) and lower HDL cholesterol (p<0.001). Higher C-peptide and insulin were associated with lower HDL cholesterol and higher triacylglycerols (p<0.001). Fasting glucose correlated with LDL cholesterol (p<0.01). Higher SHBG was associated with higher HDL and lower LDL cholesterol (p<0.001). Hormone replacement treatment was related to lower fasting blood glucose level in postmenopausal women (p<0.01). Oral contraception is suggestive of a positive influence on lipid spectrum by increasing the ratio HDL/total cholesterol. Markers of lipid and carbohydrate metabolism are not only age-related, but they are also related to BMI, total fat mass and central fat indices. Therefore, preventive programs should be focused above all on menopausal women.

Family history of diabetes mellitus determines insulin sensitivity and beta cell function in polycystic ovary syndrome.

OBJECTIVE: To examine the impact of family history of diabetes mellitus 2 (DM 2) on insulin sensitivity and secretion in lean women with polycystic ovary syndrome (PCOS). Thirteen healthy women (C), 14 PCOS without family history of DM 2 (FH-) and 8 PCOS with family history of DM 2 (FH+) were examined using euglycemic hyperinsulinemic clamp and an arginine secretion test (insulin and glucagon at fasting glycemia (AIR(FG) and AGR(FG)) and at hyperglycemia (AIR(14) and AGR(14)). FH+ women were more insulin resistant than FH- with lower insulin sensitivity index corrected per lean body mass (p 0.05). They had significantly higher triglycerides (p 0.05) and lower HDL-cholesterol (p 0.05) than C or FH- women. Concerning insulin secretion, AIR(FG) was increased in FH+ women comparing FH- women (p 0.05). Disposition indices derived from AIR(FG) or AIR(14) and insulin sensitivity index did not differ between FH+ or FH-. Thus, women with PCOS with the concomitant family history of DM 2 have lower insulin sensitivity than healthy control women. Insulin resistance observed in these women with PCOS is compensated by increased insulin secretion.

Comparison of total and salivary cortisol in a low-dose ACTH (Synacthen) test: influence of three-month oral contraceptives administration to healthy women.

The objective of this study was to evaluate the influence of low-dose combined oral contraception (COC) on basal and stimulated (1 microg ACTH test) levels of serum and salivary cortisol (F), cortisone and on basal serum cortisol binding globulin (CBG), adrenocorticotropic hormone (ACTH), dehydroepiadrosterone (DHEA) and calculated free cortisol in healthy young women. Three-month administration of COC resulted in 1) significant increase of basal (454.0+/-125.0 to 860.9+/-179.7 nmol/l) and ACTH-stimulated serum cortisol in 30th min (652.3+/-60.5 to 1374.1+/-240.6 nmol/l); 2) no significant change of basal (15.4+/-7.3 to 18.9+/-8.5 nmol/l) and ACTH-stimulated salivary cortisol at the 30th min (32.4+/-8.8 to 32.9+/-9.0 nmol/l); 3) no significant change of basal serum cortisone (38,8+/-7.68 to 45.2+/-24.2 nmol/l) and ACTH-stimulated cortisone at the 30th (34.8+/-10.9 to 47.0+/-35.7 nmol/l); 4) significant increase of basal ACTH (17.2+/-9.0 to 38.2+/-29.4 ng/l), CBG (991.0+/-161.0 to 2332.0+/-428.0 nmol/l), and 5) no significant change of basal DHEA (24.6+/-15.7 to 22.6+/-11.7 micromol/l) and calculated basal value for free cortisol (22.8+/-14.9 to 19.2+/-6.9 nmol/l). In conclusions, higher basal and ACTH-stimulated serum cortisol were found after three-month administration of COC, while basal and stimulated salivary cortisol were not significantly affected. Therefore, salivary cortisol can be used for assessment of adrenal function in women regularly using COC.

TRH test in patients with diabetes mellitus type 1 and/or autoimmune thyroiditis. Changes in the pituitary-thyroid axis, reverse T3, prolactin and growth hormone levels.

The response of the pituitary- thyroid axis, reverse triiodothyronine (rT3), prolactin, and growth hormone (GH) levels following TRH stimulus (Relefact TRH 200 microg 2 amp. i.v.) was examined in patients with autoimmune diabetes type 1 (DM1, n=30), with autoimmune thyroiditis (AT, n=25), and with concurrent DM1 and AT (n=22) to evaluate the influence of DM1 and AT of autoimmune pathogenesis on the above-mentioned hormonal parameters. Statistical analysis (ANOVA) showed that: a) the response of TSH did not differ from control groups (C); b) free triiodothyronine (fT3), free thyroxine (fT4) and their ratio in DM1, DM1+AT and C rose in 120 and 180 min, while a similar increase was not seen in AT (p<0.000001); c) rT3 was not present in any group, with rT3 levels higher in AT (p<0.00002) and lower in DM1 (p<0.02); d) the response of GH had a paradoxical character in some patients in all groups, most often in DM1 (52 %, DM1 vs C, p <0.01). The characteristic response difference was not in the peak GH level, but the delayed return to basal levels in DM1 (p<0.0001) and an abrupt one in AT (p<0.0001). The major findings in DM1 were the differences in GH response, while significant impairment of pituitary-thyroid axis and PRL response to TRH was absent. AT was associated with impairment of TRH stimulated fT3, fT4, fT3/fT4 response and changes in rT3 levels, in spite of preserved TRH-stimulated TSH secretion. GH response in AT patients was also altered.

Fasting insulin pulsatile secretion in lean women with polycystic ovary syndrome.

The aim of our study was to evaluate rapid insulin pulses and insulin secretion regularity in fasting state in lean women with polycystic ovary syndrome (PCOS) in comparison to lean healthy women. PCOS (n=8) and controls (n=7) underwent every minute blood sampling for 60 min. Insulin pulsatility was assessed by deconvolution and insulin secretion regularity by approximate entropy methodology. PCOS had higher testosterone (p<0.02), prolactin (p<0.05) and lower sex hormone binding globulin (SHBG) (p<0.0006) levels than controls. Approximate entropy, insulin pulse frequency, mass, amplitude and interpulse interval did not differ between PCOS and controls. PCOS had broader insulin peaks determined by a common half-duration (p<0.07). Burst mass correlated positively with testosterone (p<0.05) and negatively with SHBG (p 0.0004) and common half-duration correlated positively with prolactin (p<0.008) and cortisol levels (p<0.03). Approximate entropy positively correlated with BMI (p<0.04) and prolactin (p<0.03). Lean PCOS patients tended to have broader insulin peaks in comparison to healthy controls. Prolactin, androgens and cortisol might participate in alteration of insulin secretion in PCOS-affected women. Body weight and prolactin levels could influence insulin secretion regularity.

PPARgamma2 Pro12Ala polymorphism in relation to free fatty acids concentration and composition in lean healthy Czech individuals with and without family history of diabetes type 2.

Free fatty acids (FFAs) are natural ligands of the PPARgamma2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32+/-11 years; BMI 23.9+/-4.0 kg/m(2)) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels - the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARgamma2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes.

Dehydroepiandrosterone in relation to adiposity, glucose tolerance and lipid spectra in Czech non-diabetic population.

This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were enrolled into the study (women: n=235, age 28.9+/-9.4 years, BMI 22.3+/-4.5 kg/m(2), men: n=145, age 32.3+/-10.0 years, BMI 24.7+/-3.6 kg/m(2)). Spearman's correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many "beneficial" correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems -- at least in terms of its alleged antiobesity and antidiabetogenic effects -- to be more than controversial.

The UCP1 gene polymorphism A-3826G in relation to DM2 and body composition in Czech population.

UNLABELLED: Mitochondrial uncoupling contributes to the control of energy expenditure. The brown fat specific uncoupling protein 1 (UCP1) mRNA was detected in intraperitoneal and extraperitoneal adipose tissue in adult humans. The A-3826G polymorphism in the UCP1 gene promoter region was found to be associated with reduced mRNA expression indicating that the polymorphism is of functional importance. OBJECTIVE: To determine allelic frequencies and genotypic distribution of the A-3826G polymorphism and to study its possible association with anthropometric parameters and biochemical markers of glucose and lipid metabolism in type 2 diabetes mellitus (DM2) patients (n=295), in offspring of DM2 patients (n=113), and in healthy adults without family history of DM2 (n=120). RESULTS AND DISCUSSION: In the whole cohort of 528 subjects, the G allele was observed with a frequency of 0.26. Genotypic distribution did not differ between diabetics and controls. However, in the offspring of DM2 patients, significantly higher BMI and a trend towards higher waist to hip ratio, waist to height ratio, waist circumference, and subcutaneous fat mass was observed in the AG genotype compared with the wild-type. Similar tendency was evident in the control group. This indicates possible involvement of the A-3826G polymorphism in the regulation of body composition.

Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol.

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89+/-0.88 vs. 1.22+/-0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve.

Weight, body composition and fat distribution changes of Czech women in the different reproductive phases: a longitudinal study.

Women tend to gain weight with age, especially fat mass which shows also regional changes. A cross-sectional study was done on 213 Czech women with the conclusion that there is a progressive weight increase up to the menopause, an increase in absolute and relative fat contribution and fat centralisation up to the postmenopause and these changes seemed to occur even before the weight increase occurs. The same cohort was examined the same way after 3 years for further analysis. The aim was the assessment of weight gain, body composition and fat distribution changes in four age groups representing the reproductive phases in Czech women in 3-year period. 146 healthy Czech women aged 20-65 were classified according to four reproductive phases: fully reproductive women (n=34, mean age 26.96, SD 4.47), pre-menopausal women (n=34, mean age 42.23, SD 2.78), menopausal women (n=45, mean age 51.56, SD 2.61) and postmenopausal women (n=33, mean age 59.55, SD 2.82). Body weight, body composition and fat distribution were determined using classical anthropometric methods in 2000 and 2003. BMI increased significantly in all the groups except for the premenopausal group and was the greatest in the menopausal group. Increase in fat percentage was significant in the fully reproductive (p < 0.001) and menopausal women (p < 0.001), there was no change in the postmenopausal group. Waist, WHR, hip and subgluteal thigh circumference increase significantly in the menopausal group (p < 0.01, p < 0.05, p < 0.05, p < 0.001 respectively). The highest mean values of waist, WHR and even abdominal circumference remain in the postmenopausal group. Changes of all 14 skinfolds and the sum of the peripheral and central skinfolds are shown; the sum of peripheral skinfolds shows the same values at the end of the study while the sum of central skinfolds increases from the fully reproductive to the postmenopausal women. These results permit us to state the following conclusions: the greatest weight gain in the menopausal group suggests weight gain acceleration around menopause. Body fat mass increase terminates in the early postmenopause. Fat centralisation was proved in the menopausal women with still preserved fat deposition in the gluteofemoral area, which was also apparent in the postmenopausal group, however, the postmenopausal women show the highest values of central fat indicators.

Weight, body composition and fat distribution of Czech women in relation with reproductive phase: a cross-sectional study.

A sample of 213 healthy Czech women was classified into four groups according to their reproductive phase: fully reproductive, premenopausal, menopausal and postmenopausal women. Changes in body weight, body composition and fat distribution were studied in those four groups using the classical anthropometric method. Body weight rises till the menopause with no further increase. A decrease in relative contribution of muscle and bone mass was observed. The progressive increase in fat mass with age was clearly demonstrated, both the fat mass weight (r = 0.38, p < 0.001) and its percentage contribution (Matiegka r = 0.40, p < 0.001, Parízkovi r = 0.42, p < 0.001). There is a stronger correlation of central fat indices as WHR (r = 0.57, p < 0.001), abdominal (r=0.56, p < 0.001) and waist circumference (r = 0.50, p < 0.001) than for hip circumference (r = 0.27, p < 0.001) to the age. WHR and waist increase most when fully reproductive and premenopausal women were compared (p < 0.001); less when premenopausal to menopausal women are compared (NS) and the least when menopausal to postmenopausal women were compared (NS). The mean values of 14 skinfolds thickness are shown, the skinfold at the abdomen shows the strongest correlation to the age (r = 0.49, p < 0.001). The results are consistent with the hypothesis of progressive fat centralisation.

[The Endocrinology Institute celebrates its 50th anniversary. How is the Institute poised for the next 50 years?]. / Endokrinologický ústav padesátníkem Jak vstupuje do dasí padesátky?

This paper briefly describes the recent research, therapeutic and pedagogical activities of the Institute of Endocrinology in Prague, which will celebrate the 50th anniversary of its foundation in the beginning of 2007. Current research covers a broad spectrum of topics in endocrinology, which include thyroid and steroid hormone research, neuroendocrinology, immunoendocrinology, molecular endocrinology, endocrinology of aging as well as diabetes and obesity research. Not only clinical studies but also epidemiological and basic research studies are carried out at the institute. Each year approximately 25-30 research projects are conducted, financed both locally (Grant Agency of the Ministry of Health IGA, Grant Agency of the Czech Republic GACR etc.) and by foreign agencies (COST project, 6th Framework program etc.). Since the year 2000, researchers and physicians from the institute have presented 511 papers, of which 162 (32%) were published in internationally impacted journals. Almost 45 000 patients are examined each year at the three clinical departments: the Department of Clinical Endocrinology, the Obesity Management Centre and the Department of Functional Diagnostics. New diagnostic strategies such as assays of recently discovered hormones, clamp techniques, and methods of molecular biology, have been introduced into the regular clinical practice. Recent modernization of the biochemical laboratories and sampling procedures has resulted in modern facilities which offer a broad spectrum of biochemical and hormonal assessments. About 300 patients undergo laboratory investigations daily. Currently, more than half a million biochemical and hormonal assays per year are performed in the institute. The Obesity Management Centre, which was incorporated into the institute in 2002, provides a comprehensive obesity management program focused mainly on the treatment of severely obese patients and patients with high cardiometabolic risks. The institute is involved in pregraduate education at the Faculties of Medicine and at the Faculty of Science of the Charles University and at the University of Southern Bohemia. Both physicians and researchers of the institute contribute significantly to the postgraduate education in endocrinology as the institute is the seat of the Sub-Chair of Endocrinology of the Institute of the Postgraduate Education of Health Care Providers. Both the institute and the Endocrine Sub-Chair obtained the accreditation in endocrinology from the Ministry of Health. Since the acquisition of the Obesity Management Centre, the institute offers a unique one-week training program for obesity specialists organized by the Czech Society for the Study of Obesity. In the forthcoming years closer cooperation with Charles University and the Academy of Sciences is highly likely and should be reflected by a new legislative status of the Institute.

[Polyglandular activation of autoimmnunity as a manifestation of subclinical endocrinopathies]. / Polyglandulární aktivace autoimunity jako projev subklinických endokrinopatií.

BACKGROUND: Autoimmune thyropathies belong to the most frequently occurring autoimmune endocrinopathies. Autoimmune thyropathies occur either independently or linked to known polyglandular syndromes of type I-III. METHODS AND RESULTS: During the last decade, we observed a group of patients with autoimmune thyroiditis, in which autoimmune endocrinopathies were mutually associated and named the symptoms of this group "polyglandular activation of autoimmunity". The frequency of the occurrence of autoantibodies against other endocrine organs in this group was determined and the most frequent was the occurrence of the autoantibodies against steroid producing cells - anti-ovary 28 %, anti-adrenal 23 %, anti-testes 12 %. Considering the most frequent occurrence of autoantibodies against steroid producing cells, attention has been paid namely to patients with autoimmune thyroiditis and a concurrent occurrence of anti-adrenal autoantibodies. In the foreground of the clinical picture of these patients were dysregulations on the metabolic and circulation levels together with symptoms of discomfort (subfebrile condition, arthralgia and fatigue). Heavy fatigue of these patients was linked to the changes of levels and mutual ratio of melatonin and serotonin and regarding autoantibodies, mainly autoantibodies against steroid producing cells, namely against the particular cells of the layers of adrenal cortex played a role. CONCLUSIONS: The presence of autoantibodies influenced also the functional response, namely the ACTH/cortisol ratio. Autoantibodies detected were not anti-21-hydroxylase autoantibodies, typical for autoimmune polyglandular syndrome II, but antibodies against antigens of other molecular weight.

[Diabetes mellitus in adult patients with type I diabetes shows immunological, functional and clinical differences depending on the presence of autoimmune thyroiditis]. / Diabetes mellitus dospelých diabetiku 1. typu v závislosti na prítomné autoimunitní tyroiditide vykazuje imunologické, funkcní a klinické odlisnosti.

BACKGROUND: Autoimmune diabetes is usually accompanied by other autoimmune endocrinopathies, most often by autoimmune thyroiditis (AIT), but it is not clear whether diabetes in these patients differs from diabetes without AIT. METHODS AND RESULTS: Eleven-year follow-up of 47 young adult Type 1 diabetic patients with respect to the presence of AIT (group I - positive antibodies against microsomal peroxidase, antiTPO, and tyreoglobulin, antiTgl, group II - only positive antiTPO, group III - without AIT) showed: a) cessation of endogenous insulin secretion (Cpeptide <0.03 nmol/l) in 100 % of patients with AIT (in group I between year 2 and 9, in group II between year 3 and 11, p<0.05), while in group III without AIT only in 55 % of patients (I,II vs. II, p<0.001); b) higher prevalence of antiGAD values > 5 U/ml in group I when compared to patients without AIT (I vs III, p<0.05); c) tendency toward higher doses of insulin needed for diabetes compensation in patients without AIT; d) the highest prevalence of organ-specific and systemic autoantibodies in group I with the most distinct manifestations of AIT, and the lowest prevalence in group III without AIT (statistically significant). CONCLUSIONS: Autoimmune diabetes in adults with AIT compared to diabetes occurring isolated showed differences in the area of autoimmunity against islets of Langerhans, Langerhans islets' function and in the clinical course of the disease.

[Study of the genetic causes of polygeneticallv determined endocrinopathies--patience can bring success]. / Studium genetických prícin polygenne determinovaných endokrinopatií - aneb trpelivostí k úispechu.

Complex endocrinopathies, such as diabetes mellitus, obesity, polycystic ovary syndrome and osteoporosis belong to the most common diseases but their pathogenesis is still not fully explained. Environmental fadors along with genetic factors contribute to their occurrence and development. The study of genetic background is based on different strategies, mostly on linkage analysis and candidate gene approach. The common forms of these endocrinopathies do not seem to be the result of a defect of one or several major genes but the search for complex gene-gene, gene-environment interactions is needed. The article gives a short review of the recent knowledge together with our own experience in the field of study of the genetic background of polygenic diseases.

[Autoimmune polyglandular syndromes: clinical aspects]. / Autoimunitní polyglandulární syndromy: klinické aspekty.

The history of autoimmune polyglandular syndromes (APS) and the basic characteristics of types 1 and 2 are briefly introduced. The clinical aspects of the more common type 2 are discussed in more detail from the point of view of the endocrinological and diabetological practice. The diagnosis aspects of preclinical, subclinical and manifestation stage of the main diseases occurring along with APS are briefly mentioned as well as the treatments and their challenges cause by the combination of various endocrine and non-endocrine autoimmune diseases. It is emphasized that care for there patients is a life-long process and that the health condition of these patients is usually very complicated. In some cases the combination of various disease conditions can make these patients completely disabled.

Peripheral sensitivity to steroids revisited.

Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance. We have attempted to address following questions: 1) What does stay behind differences among patients as to their response to the (anti)steroid treatment? 2) Why do various tissues/cells respond differently to the same steroid hormone though they contain the same receptors? 3) Are such differences genetically dependent? The main attention was devoted to glucocorticoids as the most frequently used steroid therapeutics. Further, androgen insensitivity is discussed with a particular attention to acquired resistance to androgen deprivation therapy of prostate cancer. Finally the potential causes are outlined of breast and related cancer(s) resistance to antiestrogen therapy.

Vitamin D supplementation changed relationships, not levels of metabolic-hormonal parameters in autoimmune thyroiditis.

In women with chronic autoimmune thyroiditis and vitamin D deficiency we have found reference levels of relevant metabolic-hormonal parameters except for parathormone and total calcium. Three months supplementation with vitamin D (4300 IU/day, cholekalciferol) did not lead to significant changes of investigated hormonal parameters, while the levels of parathormone and calcium reached normal levels. However, a correlation analysis revealed marked changes in mutual relations. First, an inverse correlation of vitamin D with parathormone, insulin secretion (C peptide, insulin) and its efficiency (HOMA IR) disappeared. Relationships of vitamin D to hepatic insulin resistance (insulin/C peptide), to DHEA (both negative), and to DHEAS/DHEA ratio (positive) were newly found. Second, a positive correlation of CRP with insulin secretion remained, while its relation to insulin efficiency (HOMA IR, insulin/C peptide) was newly observed. Analogical positive correlations appeared also among anti TPO and insulinemia, insulin/C peptide, HOMA IR, and anti Tg to C peptide. A relationship of the CRP with anti TPO became significant (+). Third, out of glucose metabolism parameters only insulin/C peptide and glycemia did not correlate with vitamin D during its deficiency, while after supplementation insulin/C peptide alone correlated positively with both DHEAS and DHEA, and negatively with vitamin D.

[Incretins]. / Inkretiny.

Insulin secretion is greater after peroral challenge than after intravenous glucose administration due to so-called incretin effect. The major incretins are glucagon-like peptide 1 and glucose-dependent-insulinotropic peptide. Physiology, pathophysiology and therapeutic implications of incretins in diabetes, neurodegenerative disorders and stress-induced hyperglycemia are concerned.

[Natural antiglucocorticoids]. / Prirozené antiglukokortikoidy.

Dehydroepiandrosterone, as a sulfate after cholesterol the most abundant circulating steroid displays a number of remarkable actions, especially on immune system, where it counteracts immunosuppressive effects of glucocorticoids. Recently it has been found that in some instances the locally active agents are 7-oxygenated metabolites of this steroid, so far believed to be only degradation products. In the survey so far known effects of dehydroepaindrosterone and its metabolites are summarized on cytokine production, activation of apoptosis, their influence on macrophage migration into affected peripheral tissues, their plausible effect on angiogenesis, effects of inflammatory mediators-metabolites of arachidonic acid, and their role in the mechanism of oxidative stress. Where known, the molecular mechanisms are mentioned, staying behind these events.