Biomedical subjects

J Vrbíková

Publications and source records attributed to J Vrbíková.

At least 19 recordsLinked to original sources

PubMed2006

[The volumes of the thyroid gland in adults aged 18-65 years in the Czech Republic--determination of the norms].

OBJECTIVE: In the areas with moderate iodine deficit the sonographic examination of thyroid gland is a precious method of precise determination of its volume. The objective of the work was the sonographic examination of males and females aged 18-65 years and to determine the norms of the volumes of thyroid gland. METHODS AND RESULTS: In total, by random sampling, there were sonographically examined 3 416 adults in 11 areas of the Czech Republic; there was chosen a set of 971 females and 681 males whose iodinuria level in first morning urine sample was equal or higher than 100 microg/l. This set was divided according to sex and into the age categories in 5-year interval. The measurement of 3 dimensions of the thyroid gland was determined by Medison-Kretz SA 600 sonographic device with the use of 7.5 MHz linear probe for the depth and width measurement and 3.5 MHz probe was used for the lengths measurement. The volume was determined for each lobe individually using Brunn's formula: V (ml) = 0.479 x length x depth x width. Our results imply the age-related increase of the volume of thyroid gland at both sexes (F-ratio = 1.99, p < 0.0001). At men and women the volume of thyroid gland fluently increases to the 30th year equally, from 30 years to 55 years it increases more rapidly in men while in women there is observed a moderate plateau. Further increase of the volume of thyroid gland is equally fluent from the age of 55 years. CONCLUSION: We managed to determine first own norms of the volumes of thyroid gland for men and women aged 18-65 years in the Czech Republic in five-year age categories. In terms of practical use we recommend 90th percentile as a limit for the evaluation of upper limit of thyroid gland and the 10th percentile for the evaluation of lower limit of the volume of thyroid gland.

Adolescent↗

PubMed2006

[Thyroid autoimmunity in adults with diabetes mellitus type 1. Own experience gained by 11-year monitoring].

The results of study on thyroid autoimmunity and its clinical importance gained during 11-year follow-up of 47 adults with type 1 diabetes mellitus (DM1) are presented. The study proved the preponderance of women among subject affected with thyroid autoimmunity, the autoantibodies against thyroid gland (T-Ab) were significantly more often detected in women compared to men (68% vs. 32%, p < 0.05). Also, serious forms of thyroid autoimmunity manifested with persistence of both T-Ab, faster development of subclinical hypothyroidism (TSH > 4.5 mIU/l in 100% within 4 years after first detection of T-Ab positivity, and within 8 years after DM1 manifestation, respectively), and diffuse hypoechogenic pattern at thyroid gland ultrasonography (USG) were significantly more often observed in women compared to men (45% vs. 12%, p < 0.01). These patients often had small thyroid gland (77% of subjects had volume below 25th percentile of control subjects at the 11th year of follow-up) and presence of thyreopathy in the first degree relatives. No difference between men and women was observed in persistence of thyroid peroxidase autoantibodies (anti-TPO) solely (20% vs. 23%); milder clinical course of thyroid disease was observed in these subjects (the fist detection of TSH > 4.5 mIU/l in the 9th year of follow-up). These patients had varied findings at USG examination with focally/diffuse hypoechogenic/ non-homogenous thyroid gland, and 50% of subjects had thyroid gland volume above 95th percentile in the 11th year of follow-up. Among subjects without thyroid autoimmunity men prevailed (68% vs. 32% women, p < 0.01), and in the 11th year of follow-up the USG finding was often abnormal (thyroid gland volume above 95th percentile of the controls in more than 60% of subjects, trend towards nodulisation). Except for 1 subject, TSH did not exceed 4.5 mIU/l. These results obtained from the Czech population constitute the basis for our recommendation to screen regularly markers of thyroid autoimmunity in patients with DM1. Ultrasonographic examination, that is able to detect sings of thyroid immunopathy in many subjects before first manifestation of T-Ab, is the most sensitive according to both our experience and the published data. For clinical practice, determination of TSH once a year in all DM1 subjects, and of anti-TPO in DM1 women in fertile age is recommended. Ultrasonographic examination should be carried out in case of pathologic results of these tests.

Adult↗

PubMed2006

[Incretins].

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.

Animals↗

PubMed2005

Metabolic syndrome in young Czech women with polycystic ovary syndrome.

METHODS: Sixty-nine young women with polycystic ovary syndrome (PCOS) [age 25.2+/- 4.7 years, with body mass index (BMI) 24.3 +/- 4.8 kg/m2; mean 6 SD] and 73 age-matched healthy females (BMI 22.3 +/- 3.3 kg/m2; mean +/- SD) were evaluated for the occurrence of features of metabolic syndrome according to the Adult Treatment Panel III. RESULTS: Overt metabolic syndrome (the presence of three and more risk factors) was not more common in PCOS women (1/64, 1.6%) than in healthy controls (0/73, 0%). On the other hand, in nearly 50% of PCOS women isolated features of metabolic syndrome, most often a decrease in high-density lipoprotein (HDL) cholesterol, were found. Women with at least one feature of metabolic syndrome were, in comparison with women without any of these features, significantly more obese (P = 0.0001), with lower insulin sensitivity (P = 0.05). When comparing PCOS women according to the degree of insulin sensitivity, as determined by euglycaemic clamp, isolated features of metabolic syndrome were found in 8/17 women above the upper quartile, compared with 11/16 women below the lower quartile of insulin sensitivity (P = 0.20). CONCLUSIONS: Overt metabolic syndrome is only rarely encountered in young Czech females affected by PCOS but its isolated features are relatively frequent, both in young PCOS patients and in age-matched control women.

Adult↗

PubMed2005

Combined oral contraceptives in the treatment of polycystic ovary syndrome.

Combined oral contraceptives (COC) are the most often used treatment modality for polycystic ovary syndrome (PCOS). Undisputedly, COC suppress androgen production, thus ameliorating skin androgenic symptoms and improving menstrual dysfunction. On the other hand, there are still many unresolved issues concerning their metabolic effects. COC could decrease insulin sensitivity and deteriorate glucose tolerance, although the negative influence on insulin sensitivity is dependent on other factors (especially obesity) and this need not be expressed in non-obese patients. It is probable that the impairment of glucose tolerance is reversible, as the incidence of diabetes is not increased in past COC users. The effects of COC on the lipid spectrum are dependent on the type of gestagen, but lipid levels usually remain within the reference limits. Combination therapy of COC with weight reduction or insulin sensitizers could further suppress androgen levels and improve metabolic parameters. The establishment of COC after laparoscopic ovarian drilling may further decrease androgen levels. The combination of COC and GnRH analogues is not superior to COC therapy alone. Prospective data about the influence of COC on the risk of diabetes mellitus, coronary artery disease and endometrial cancer in PCOS women are lacking.

Contraceptives, Oral, Hormonal↗

PubMed2005

Differences in type I diabetes mellitus of young adults with and without thyroid autoimmunity.

This work was intended to study if the coexistence of thyroid and Langerhans islets autoimmunity is associated with a different nature and course of diabetes in young adult diabetic patients. We followed the laboratory and clinical course of diabetes and the thyroid gland status of 47 young adults with Type I diabetes over a 9-year period starting from the onset of diabetes (ranging from 18 to 35 years of age). The patients were divided into subgroup I (with thyroid peroxidase and thyroglobulin antibodies, n = 13), subgroup II (thyroid peroxidase antibody only, n = 10), and subgroup III (without thyroid autoimmunity, n = 24). Out of the 22 females followed, 10 (46 %) and 5 (23 %) were in subgroups with thyroid autoimmunity (TA), I and II, respectively. On the contrary, out of the 25 men followed, 17 (68 %) were in group III. Within the 9 years, insulin secretion nearly ceased (C-peptide < 0.03 nmol/L) in all of the patients of subgroup I and 70 % of subgroup II, but only in 46 % of patients in subgroup III (I : II p < 0.01, I : III, p < 0.01, II : III, p < 0.05). The cumulative incidence of antiGAD > 1 U/mL (CIS, RIA) in subgroup I was higher (92 %) than in subgroups II (80 %) and III (53 %); I : III, p < 0.05. The cumulative incidence of tyrosine phosphatase antibodies (anti-IA2, BRAHMS, RIA) was insignificantly higher in subgroups I and II when compared with subgroup III (62 %, 60 %, and 42 %). The study of organ-specific and systemic autoantibodies showed their highest cumulative incidence in subgroup I, i.e., in patients with the most expressed manifestations of TA and the lowest one in subgroup III, i.e., diabetic patients without TA. Our results suggest that overall thyroid autoimmunity in young adult patients with Type I diabetes was associated not only with female gender, but also with more pronounced Langerhans islets autoimmunity and significantly faster cessation of endogenous insulin secretion; it was associated with therapeutical doses of insulin as well.

Adolescent↗

PubMed2004

Flutamide suppresses adrenal steroidogenesis but has no effect on insulin resistance and secretion and lipid levels in overweight women with polycystic ovary syndrome.

The authors evaluate the effects of 2 months of treatment with 250 mg flutamide daily on adrenal steroidogenesis (ACTH test) and metabolic parameters (lipids, insulin resistance) in 12 PCOS women aged 33.8 +/- 7.5 years and with a BMI of 33.6 +/- 4.2 kg/m2. Significant decreases in basal DHEA-S (p < 0.0001), DHEA (p < 0.01) and androstenedione (p < 0.05), in the ACTH-stimulated levels of DHEA-S (p < 0.0001), testosterone (p < 0.05) and in ACTH-stimulated 17beta-hydroxysteroid dehydrogenase activity (p < 0.01) were observed. No significant change in basal blood glucose, insulin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides or in insulin resistance, as estimated by the insulin tolerance test, was found. Flutamide is effective in reducing adrenal androgen production in overweight women, but has no effect on lipid spectrum or on insulin resistance.

17-Hydroxysteroid Dehydrogenases↗

PubMed2004

Thyroid autoantibodies and their clinical relevance in young adults with type 1 diabetes during the first 12 yr after diabetes onset.

In order to obtain prospective data on occurrence of thyroid autoantibodies [against thyroid peroxidase (antiTPO) and against thyroglobulin (antiTgl)] and their clinical relevance, we followed up on 109 young adults with Type 1 diabetes for 12 yr after diabetes onset. The patients were divided into subgroup I [positivity of both thyroid autoantibodies (T-Ab); 25%, women predominantly], subgroup II (isolated antiTPO positivity only, 26%, men and women equally) and subgroup III (thyroid autoimmunity not present, 49%, men mainly). Cumulative incidence of T-Ab during the 12 yr of follow-up was 51% with predominance of women over men (65% vs 38%, p<0.01). At the time of the first T-Ab detection, an ultrasonography pattern of a hypoechogenic thyroid gland was noted in 59% of subgroup I patients and in 25% of subgroup II patients (p<0.05). At the same time, TSH>4.5 mlU/I was shown in 30 and 7% of patients of subgroups I and II, respectively (p<0.05). In the patients with the repeated positivity of both T-Ab (subgroup I) subclinical hypothyroidism developed in all patients within 4 yr after the first detection of T-Ab. On the contrary, the clinical course in patients with isolated antiTPO positivity (subgroup II) was milder with 11% developing subclinical hypothyroidism within 4 yr after the first antiTPO detection (p<0.001). The data shed new light on the relative diagnostic value of thyroid antibodies, ultrasonography and functional examination for an early detection of thyroid autoimmunity of adult diabetic patients.

Adolescent↗

PubMed2004

Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Twenty-four women with PCOS, aged 25.4+/-4.3 (mean+/-s.d.) years, body mass index 24.5+/-3.9 kg/m2 were randomly assigned to receive either transdermal oestradiol plus CPA (n=12) or a peroral oestradiol-CPA combination (n=12). Before and after 3 months of treatment, basal blood samples, euglycaemic hyperinsulinaemic clamp combined with indirect calorimetry and arginine tests were performed. ANOVA and Student's t-test or Wilcoxon's test were used for statistical analyses. RESULTS: After peroral oestradiol-CPA, insulin sensitivity (P<0.004) and the disposition index as the function of insulin sensitivity and secretion (P<0.0001) decreased significantly. Fasting insulin (P<0.05), cholesterol (P<0.05), high-density lipoprotein cholesterol (P<0.05) and sex-hormone binding globulin (P<0.0001) increased significantly. Dehydroepiandrosterone (P<0.05) and 17-OH progesterone (P<0.01) decreased significantly. After transdermal oestradiol+CPA, no significant changes were observed in sex-hormone binding globulin and androgen concentrations, insulin sensitivity or disposition index. CONCLUSIONS: In women with PCOS, peroral oestrogens (at doses common in combined oral contraceptives) led to a significant impairment in insulin secretion and action. In contrast, the transdermal application of oestrogens did not significantly influence insulin sensitivity.

Administration, Cutaneous↗

PubMed2003

Cardiovascular risk factors in young Czech females with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) could be associated with a variety of signs of metabolic syndrome. The aim of our study was to compare the cardiovascular risk factors in PCOS women and in a control group selected from a random population sample. METHODS AND RESULTS: 50 PCOS women with a mean (+/-SD) age of 30.7 +/- 4.2 years, and 335 controls with a mean age of 29.9 +/- 3.1 years selected from a random population sample of nine districts of the Czech Republic were compared for basic anthropometric characteristics, blood pressure, plasma lipids and fasting glucose. PCOS women had a significantly higher body mass index (BMI). After adjusting for BMI, PCOS women had higher blood pressure and LDL-cholesterol, and lower HDL and HDL-cholesterol/total ratio. Arterial hypertension was more prevalent in PCOS women than in controls. There was no difference in the prevalence of impaired fasting glucose between both groups. Impaired glucose tolerance was found in 11.8% of PCOS women. Diabetes mellitus was more frequent in PCOS families. CONCLUSIONS: Czech PCOS women, even in their thirties, show a significantly worse cardiovascular risk profile than a control group selected from a random population sample. The differences cannot be explained by obesity.

Adult↗

PubMed2002

[Metformin has a positive effect on disorders of carbohydrate metabolism in long-term care with low doses of prednisone].

BACKGROUND: The influence of long-term, low doses of prednison administration (< 0.3 mg/kg/day) on glucoregulation and glucose tolerance was studied in 20 female patients (15-20 yrs), including verification of possibility to correct the impairment of glucose tolerance (IGT) by metformin (M). METHODS AND RESULTS: During prednison treatment, we found typical signs of insulin resistance manifestation: HOMAIR 3.55 (5.13), blood insulin/glucose ratio 3.8 (5.84), QUICKI 0.61 (0.124). These were associated with higher Langerhans (L.) islets hormone secretion detected under basal conditions as well as after bolus of 5 g arginine chloride. However, detailed analysis of hormone secretion ratios revealed distinct signs of L. islets function impairment and subcompensation. Specifically, low ratio C peptide/proinsulin and C peptide/glucagon were characteristicaly observed. Six months of M. administration (1000 mg/day) had a beneficial effect on glucose metabolisms deviations as indicated by the following: insulin resistance decreased (HOMAIR 1.96 (1.60), insulin/glucose ratio 2.34 (1.52), QUICKI increased at 0.699 (0.238)). At the same time we found a decrease in the basal levels of insulin, proinsulin, glucagon, C peptide and amyline, and AUC proinsulin and glucagon as well. HOMAsecretion decreased from an initial value of 389 (376) to 207 (119). CONCLUSIONS: Judging by the new hormonal secretion ratios, the L. islets' function following M. treatment substantially improved. From the clinical point of view, it is important to note that M. was tolerated very well. No patient interrupted the follow up because of M. intolerance. IGT in the whole group normalised, in spite of the fact that no accent was put on the regime, diet including. The 90% of lactate values did not exceed 1.7 mmol/l. Based on the results, we may conclude that M. has a beneficial effect on long-term, low doses of glucocorticoid-related (induced) glucose metabolism impairment, and therefore, M. administration could be recommended, particularly in the situations with higher levels of glycosylated hemoglobin.

Adolescent↗

PubMed2002

[Role of the steroids, SHBG, IGF-1, IGF BP-3 and growth hormone in glucose metabolism disorders during long-term treatment with low doses of glucocorticoids].

BACKGROUND: The relationships between selected steroids, SHBG, growth hormone, IGF-1, IGF BP-3 and indicators of glucose metabolism were studied in the group of 20 female patients (15-20 yrs) on long-term treatment with low prednisone doses (< 0.3 mg/kg/day) (baseline phase) and after adding 1000 mg of metformin per day for following 6 months to improve impaired glucose metabolism (control phase). METHODS AND RESULTS: Lower basal DHEAS and DHEA (DHEA/S) levels were found as compared with reference values. Only DHEAS level returned into the reference range after the treatment with metformin. Decrease of DHEA/S depended on the doses (DHEAS -0.7621, DHEA -0.7685). Positive correlations between DHEA/S and of the results insulin tolerance were found as at the baseline (+0.4452, resp. +0.4455) as well as in the control period after the metformin administration (+0.7549, resp. +0.6073). Testosterone (T) and dihydrotestosterone(DHT) values were within the reference range during the whole study. Due to very low SHBG levels higher free androgen index (FAI) was recorded in more than half of the patients. Significant relationships were revealed between former gonadal androgens and indicators of glucose metabolism deterioration at the control phase: T correlated: with fasting insulin (+0.6005), with HOMAIR (+0.5380), with insulin/glucose (+0.5261), with fasting glucose (+0.9268), with AUC glucose (+0.6792), FAI: with fasting insulin (+0.5560), with HOMAIR (+0.5269), with fasting glucose (+0.9025), with AUC glucose (+0.7143), DHT: with fasting C peptide (+0.7921), with AUC C peptide (+0.7143). SHBG correlated: with fasting glucose (-0.6519), and with AUC glucose (-0.5868). The tendency of GH to lower, and IGF-1, IGF BP-3 to higher values at the baseline changed at the control phase: fasting and AUC value of GH increased (signif.), while were IGF-1 (nonsignif.) and IGF BP-3 (signif.) levels decreased. Surprisingly, no correlation was observed between GH and parameters of glucose metabolism. Contrary to GH, baseline IGFBP-3 values correlated: with HOMAIR (+0.5002), with insulin/glucose (+0.4860). The same relationships were found between AUC IGF BP-3 (+0.5676, +0.5559), IGF-1 (HOMAIR only +0.5412), IGF-1/IGF BP-3 (+0.5059, +0.5716) and parameters of insulin sensitivity (HOMAIR, insulin/glucose) in the control period. For the first time negative correlations between IGF-1, IGF-1 AUC, IGF BP-3, IGF-1/IGF BP-3 and somatostatin blood levels were discovered at the control phase. CONCLUSIONS: The study brought a number of new information about the importance of the "non-classical" glucoregulatory hormones in impairment of glucose metabolism, during long-term administration of low prednisone doses. The results suggest, that without normalisation of low DHEA/S, SHBG and high FAI levels it would not be possible to correct glucose metabolism properly in patients with long-term glucocorticoid therapy.

Adolescent↗

PubMed2002

Autoimmune thyroiditis in non-obese subjects with initial diagnosis of Type 2 diabetes mellitus.

Autoimmune thyroiditis is often associated with Type 1 diabetes mellitus (T1DM). In non-obese adult-onset diabetes diagnosed initially as Type 2 diabetes mellitus (T2DM), there is a proportion of cases with so far undiagnosed T1DM. The objective of this study was to estimate the frequency of autoimmune thyroiditis (AT) among non-obese (BMI <30.0 kg/m2) patients with T2DM and to compare the frequency of AT in subgroups of patients according to the presence of glutamic acid decarboxylase antibodies (GADA), insulin requirement, and post-breakfast C-peptide levels. The study included 118 adult patients (55 men and 63 women) with the initial diagnosis of T2DM and age at the onset of diabetes > 35 yr. Median of age was 66 yr (range 39-82), and median duration of diabetes was 9 (range 1-27) yr. AT was diagnosed using thyroid peroxidase antibodies, TG-antibodies, US and TSH levels. Nineteen per cent of the subjects were found to have AT, and the frequency of AT did not significantly differ between the groups of GADA+ and GADA- subjects. There was no difference in the frequency of AT between the group treated with hypoglycemic agents and/or diet and the group requiring insulin. The frequency of AT was higher in the group with post-breakfast C-peptide levels < or = 0.8 nmol/l compared to the group with post-breakfast C-peptide levels > 0.8 nmol/l (37% vs 16%), however the group with post-breakfast C-peptide levels < or = 0.8 nmol/l had longer duration of diabetes.

Adult↗

PubMed2002

Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome.

UNLABELLED: Risk for atherosclerosis is increased in women with polycystic ovary syndrome (PCOS). Homocysteine (Hcy) is one of the independent risk factors for ischemic heart disease. We examined the effect of metformin (M) treatment on Hcy levels, steroids and glycide tolerance in PCOS. MATERIAL AND METHODS: 9 women with PCOS (defined as hyperandrogenemia and chronic anovulation); age 20 +/- 3.8 yrs, BMI 28.1 +/- 6.5 kg/m(2); examined in the follicular phase of spontaneous menstrual cycle before and after 27 +/- 4 weeks of treatment with M 1000 mg/day. The plasma concentrations of Hcy, DHEA, DHEA-S, cortisol (F), allopregnanolone (HPO), 17OHpregnenolone (17OHPl), insulin (I) and blood glucose (G) before and after the course of M were measured. RESULTS: After the course of M, Hcy significantly increased (10.1 +/- 2.6 to 13.4 +/- 5.1 micromol/l, p < 0.05.). There was no significant change in levels of I, HPO, F, DHEA-S and 17OHPl. DHEA levels increased significantly (from 26.9 +/- 15.7 to 44.4 +/- 24.6 nmol/l, p < 0.05). A borderline significant trend towards reduction in waist-hip ratio was seen (from 0.986 +/- 0.042 to 0.951 +/- 0.085; p < 0.06). CONCLUSIONS: Treatment with metformin in women with PCOS can lead to the increase in homocysteine levels--a risk factor for atherosclerosis.

17-alpha-Hydroxypregnenolone↗

PubMed2002

Prediction of the effect of metformin treatment in patients with polycystic ovary syndrome.

The objective of the study was to find predictors of a successful therapy with metformin in polycystic ovary syndrome. 24 women with polycystic ovary syndrome were examined (oral glucose tolerance test and gonadotropin-releasing hormone analogue test) before and after a 6-month course of metformin (1 g/day). In 58% of the women, a significant improvement in the menstrual cycle pattern was observed. After a treatment course, a significant reduction in gonadotropin-releasing hormone analogue stimulated levels of testosterone (p < 0.05), free testosterone index (p < 0.01), luteinizing hormone (p < 0.05), and estradiol (p < 0.01) was found. The best prediction of the improvement in menstrual cyclicity after metformin was achieved with a combination of basal values of 17-hydroxyprogesterone, testosterone, sex hormone binding globulin, and androstenedione. These variables correctly classified 86.7% of the responders. The best predictor of changes in the index of free testosterone after metformin treatment was the combination of estradiol and androstenedione in the gonadotropin-releasing hormone analogue test, with basal testosterone correctly classifying 91.7% of the subjects.

Female↗

PubMed2001

[Effect of long-term treatment with metformin on steroid levels and parameters of insulin resistance in women with polycystic ovary syndrome].

BACKGROUND: Insulin resistance is probably the key factor in the pathogenesis of polycystic ovary syndrome, and thus insulin sensitization can be a beneficial treatment. We tried to investigate effects of long-term therapy with metformin in polycystic ovary syndrome on steroid levels, ovarian steroidogenesis and on insulin resistance and secretion. We also tried to find predictors of the successful therapy (in terms of improvement of menstrual cyclicity). METHODS AND RESULTS: 24 oligo/amenorhoeic women with polycystic ovary syndrome were included into the study. Basal blood samples were taken for the determination of testosterone, estradiol, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulphate, 17OH progesterone, 17OH pregnenonole, sex-hormone binding globulin and cortisol. Gonadoliberin (GnRH) analogue test was performed with estimation of the same steroids and LH. Oral glucose tolerance test was done with dextrose, and with estimation of glucose, insulin, and C peptide. HOMA model assessment was used for calculation of insulin resistance and insulin secretion. All examinations were done before and after 27 +/- 4 weeks (average +/- standard deviation) of therapy with metformin 1000 mg/day. Significant improvement in menstrual cyclicity was observed in 58% of women. No significant change in basal steroid levels was found. A trend towards decline in insulin resistance and secretion was detected. Significant decrease in the mean stimulated testosterone level (from 1.74 to 1.54 nmol/l, 95% CI 1.42-2.08 and 1.21-1.87; p < 0.05), 17OH progesterone level (from 3.32 to 2.37, 95% CI 1.42-2.08 and 1.21-1.87; p < 0.05), LH (from 9.1 to 4.8 IU/l, 95% CI 6.4-12.8 and 3.4-6.8; p < 0.05), and estradiol level (from 0.91 to 0.43 nmol/l, 95% CI 0.69-1.19 and 0.38-0.65; p < 0.01) were detected. The best prediction of the improvement in menstrual cyclicity after metformin was achieved with the combination of basal 17OH progesterone, androstendione, testosterone and SHBG. This model correctly classified 86.7% of subjects. CONCLUSIONS: Long-term therapy with metformin led to the improvement in menstrual cyclicity, without significant change in basal steroid levels or parameters of insulin resistance.

17-alpha-Hydroxypregnenolone↗

PubMed2001

The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS: Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. RESULTS: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01). CONCLUSIONS: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.

Adrenal Glands↗

PubMed1996

[Thyroglobulin and microsome autoantibodies and their clinical significance in adult type I diabetics].

In 34 patients with type 1 diabetes manifested in postadolescent age (mean age at time of diagnosis 25 years, 18 women and 16 men) after the establishment of the diagnosis perspectively the presence of antibodies against thyroglobulin and the microsomal fraction and their relation to affection of the thyroid gland was investigated. During an investigation of 20% of the patients the authors provided repeatedly evidence of the presence of both antibodies, in 23% repeatedly only against microsomes. In 21% some antibodies were detected only once. In the course of the investigation in 65% of the patients thyroid antibodies were found. The clinically most serious affection of the thyroid gland (from the sonographic an functional aspect) was found in groups 1 an 2, while in groups 3 and 4 in the majority of patients the thyroid gland was not affected. A different pathogenesis of the disease in the above groups is suggested in the areas of DR and DQ during HLA typing, the behaviour of other antibodies and differences in dermatoglyphic examinations. Moreover there is a high ratio of women in the first two groups (61%) and conversely of men in groups 3 and 4. In the discussion attention is drawn to the different course of diabetes in patients with thyroid autoimmunity.

Adult↗