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Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on hypothalamic-pituitary-thyroid axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.

Background Metformin was found to reduce circulating levels of pituitary hormones. Objective The purpose of this study was to assess whether sex determines the effect of metformin on lactotroph secretory function. Methods The study population included 25 women and 12 men with mildly elevated serum prolactin levels (25–75 ng/mL). Because of concomitant type 2 diabetes, all participants were treated with metformin (3 g daily). Plasma levels of glucose and lipids, HOMA1-IR, serum levels of prolactin, thyrotropin and free thyroid hormones, as well as Jostel’s, SPINA-GT and SPINA-GD indices were assessed at baseline and at the end of metformin treatment. Results The study completed 24 women and 11 men. At baseline, there were no significant differences in circulating levels of glucose and lipids, insulin sensitivity, hormones, Jostel’s, SPINA-GT and SPINA-GD indices between women and men. In both men and women, metformin reduced fasting glucose levels and HOMA1-IR. However, only in women metformin decreased elevated prolactin levels and this effect correlated with an improvement insulin sensitivity, as well as with the impact on SPINA-GT. Conclusions The results of the study suggest that the effect of metformin on serum prolactin levels is sex-dependent.

Background: No previous study has investigated cardiometabolic risk factors in untreated patients with congenital adrenal hyperplasia (CAH).Methods: The study population consisted of 14 premenopausal women with previously untreated non-classic congenital adrenal hyperplasia (NC-CAH) and 20 matched healthy women. Apart from 17-hydroxyprogesterone and androgen levels, the outcomes of interest were glucose homeostasis markers, plasma lipids, plasma levels of uric acid, C-reactive protein, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR).Results: As expected, women with NC-CAH were characterised by higher levels of 17-hydroxyprogesterone and were more insulin-resistant than control women. The mean values of C-reactive protein, fibrinogen, homocysteine and UACR were higher while 25-hydroxyvitamin D levels were lower in subjects with NC-CAH. The investigated cardiometabolic risk factors correlated with androgen levels and insulin sensitivity.Conclusions: The obtained results suggest that the occurrence of NC-CAH in premenopausal women may increase cardiometabolic risk.

WHAT IS KNOWN AND OBJECTIVE The impact of metformin on thyrotropin levels is sex-dependent. No previous study has assessed whether sex steroids determine metformin action on thyrotrope and thyroid cell functioning. The aim of the present study was to compare the effect of this agent on hypothalamic-pituitary-thyroid axis activity and thyroid function tests between women receiving oral contraceptive pills and women not using any contraception. METHODS The study population included 52 women with subclinical hypothyroidism and prediabetes or diabetes, 20 of whom had been using oral contraceptive pills for at least 12 months before the beginning of the study. Over the entire study period (4 months), all participants received oral metformin (1.7-3 g daily). Circulating levels of glucose, insulin, thyrotropin, free thyroid hormones, oestradiol, gonadotropins and prolactin were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning and at the end of the study. RESULTS AND DISCUSSION The study groups differed in oestradiol, gonadotropins and prolactin levels and in structure parameter inference approach (SPINA)-GT. In both groups, metformin reduced glucose levels, homeostasis model assessment 1 of insulin resistance index (HOMA1-IR), thyrotropin levels and Jostel's thyrotropin index, as well as increased SPINA-GT. In women receiving oral contraceptive pills, the drug slightly decreased serum prolactin levels. The impact on metformin on HOMA1-IR, thyrotropin, prolactin, Jostel's thyrotropin index and SPINA-GT was more pronounced if women received oral contraception, as well as more pronounced in patients treated with higher doses of this agent. Treatment-induced changes in thyrotropin and Jostel's thyrotropin index correlated with their baseline values, baseline levels of oestradiol and gonadotropins, as well as with the degree of a reduction in HOMA1-IR. WHAT IS NEW AND CONCLUSION This study is the first one to have shown that oral oestrogens potentiate the effect of metformin on hypothalamic-pituitary-thyroid axis activity.

Obesity and diabetes mellitus (DM) are common disorders that increase cardiovascular risk and lead to coronary artery disease (CAD).The aim of our study was to assess the link between epicardial fat (EF) volume and paracardial fat (PF) volume, relative expressions of several genes in epicardial, paracardial, and perivascular fat and corresponding serum cytokines in patients with CAD in relation to DM.A total of 66 consecutive patients (33 with DM) with multivessel CAD were included. We obtained cardiac magnetic resonance, serum cytokines levels, and their relative mRNA expressions in EF, PF, and perivascular fat samples of the following: adrenomedullin (ADM), fibroblast growth factor 21 (FGF21), transforming growth factor β (TGFβ), phospholipid transfer protein (PLTP), receptor for advanced glycation endproducts (RAGE), thrombospondin 1 (THSB1), and uncoupling protein 1 (UCP1).There were no differences in the anthropometric parameters or fat depots, except for higher epicardial fat volume in patients with DM (mean [SD], 105.6 [38.5] ml vs 84 [29.2] ml; P = 0.02). Patients with DM exhibited a significantly increased RAGE expression in EF (median [Q1-Q3], 0.17 [0.06-1.48] AU vs 0.08 [0.02-0.24] AU, P = 0.03). Diabetes was also associated with increased expression of ADM in EF and PF and decreased expression of FGF21 compared with patients without DM.Patients with multivessel CAD and DM revealed increased volume and more dysfunctional profile of gene expressions in EF and significantly decreased expression of cardioprotective FGF21.

INTRODUCTION Obesity and diabetes mellitus (DM) are common disorders that increase cardiovascular risk and lead to coronary artery disease (CAD). OBJECTIVES The aim of our study was to assess the link between epicardial fat (EF) volume and paracardial fat (PF) volume, relative expressions of several genes in epicardial, paracardial, and perivascular fat and corresponding serum cytokines in patients with CAD in relation to DM. PATIENTS AND METHODS A total of 66 consecutive patients (33 with DM) with multivessel CAD were included. We obtained cardiac magnetic resonance, serum cytokines levels, and their relative mRNA expressions in EF, PF, and perivascular fat samples of the following: adrenomedullin (ADM), fibroblast growth factor 21 (FGF21), transforming growth factor β (TGFβ), phospholipid transfer protein (PLTP), receptor for advanced glycation endproducts (RAGE), thrombospondin 1 (THSB1), and uncoupling protein 1 (UCP1). RESULTS There were no differences in the anthropometric parameters or fat depots, except for higher epicardial fat volume in patients with DM (mean [SD], 105.6 [38.5] ml vs 84 [29.2] ml; P = 0.02). Patients with DM exhibited a significantly increased RAGE expression in EF (median [Q1-Q3], 0.17 [0.06-1.48] AU vs 0.08 [0.02-0.24] AU, P = 0.03). Diabetes was also associated with increased expression of ADM in EF and PF and decreased expression of FGF21 compared with patients without DM. CONCLUSIONS Patients with multivessel CAD and DM revealed increased volume and more dysfunctional profile of gene expressions in EF and significantly decreased expression of cardioprotective FGF21.

Cardiovascular diseases are among the leading causes of increased morbidity and mortality in developed and developing countries. One of the most important risk factors responsible for atherosclerosis and subsequent cardiovascular diseases is hyperlipidaemia. Currently, hyperlipidaemias are divided into several clinical entities. The greatest risk is associated with hypercholesterolaemia. As a result, modern guidelines for the treatment and prevention of atherosclerosis focus predominantly on the reduction of LDL-cholesterol. Hypertriglyceridaemia and atherogenic dyslipidaemia, which are responsible for a less significant increase in the cardiovascular risk, are nowadays secondary targets of the treatment. During the work-up for hyperlipidaemia one of the essential actions is the exclusion of secondary causes of the lipid abnormalities. Those include, among others, endocrine diseases, diabetes, drugs, nephrotic syndrome, and pregnancy. Data regarding the impact of endocrine disease and diabetes on the lipid profile are scattered. In this review, the authors aimed to perform a thorough analysis of the available publications regarding the topic and the preparation of a comprehensive review dealing with the incidence, clinical features, and the therapy of hyperlipidaemias in patients with endocrine disease.

WHAT IS KNOWN AND OBJECTIVE Cardiometabolic effects of hypolipidaemic agents depend on plasma levels of monomeric prolactin. Although macroprolactinaemia seems to be associated with increased cardiometabolic risk, no previous study has investigated whether macroprolactinaemia modulates pleiotropic effects of hypolipidaemic agents. METHODS The study population included two age-, weight-, blood pressure- and lipid-matched groups of men: 12 men with elevated levels of big-big prolactin and 16 men with prolactin levels within the reference range. Because of atherogenic dyslipidaemia, all subjects were treated for 6 months with fenofibrate (200 mg daily). Glucose homeostasis markers and plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D, were determined in patients at the beginning and at the end of the study. RESULTS AND DISCUSSION Men with elevated levels of big-big prolactin were characterized by higher levels of hsCRP and fibrinogen and lower levels of 25-hydroxyvitamin D as well as decreased insulin sensitivity than subjects with prolactin levels within the reference range. In men without macroprolactinaemia, fenofibrate decreased circulating levels of total and LDL cholesterol, triglycerides, uric acid, hsCRP and fibrinogen, and increased concentrations of HDL cholesterol, homocysteine and 25-hydroxyvitamin D, as well as improved insulin sensitivity. In subjects with macroprolactinaemia, fenofibrate action was limited to the changes in HDL cholesterol, triglycerides, hsCRP and homocysteine. With the exception of homocysteine, cardiometabolic effects of fenofibrate were stronger in subjects without than in subjects with elevated levels of big-big prolactin. WHAT IS NEW AND CONCLUSION The results of the study indicate that macroprolactinaemia exerts a negative impact on cardiometabolic effects of fenofibrate.

Background Metformin reduced prolactin levels only in women with hyperprolactinemia. Objective The purpose of this case-control study was to compare metformin action on lactoctrope function between women receiving oral contraceptive pills and women not using hormonal contraception. Methods The study included two groups of matched women with elevated prolactin levels and new-onset prediabetes or diabetes. The first group consisted of 20 women using oral contraceptive pills for at least 12 months before entering the study, while the second group included 20 patients not using any hormonal contraception. Over the whole study period, all women were treated with metformin (1.7–3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, adrenocorticotropic hormone, gonadotropins and insulin-like growth factor-1 were measured at the beginning and at the end of the study (16 weeks later). Results Thirty-eight patients completed the study. Metformin reduced plasma glucose levels and improved insulin sensitivity but the latter effect was stronger in women receiving oral contraceptive pills than in women not using any contraception. Although metformin treatment decreased plasma prolactin levels in both study groups, this effect was stronger in women taking oral contraceptive pills. Only in this group of women, metformin increased plasma luteinizing hormone levels. The changes in plasma prolactin correlated with their baseline insulin sensitivity and the effect of metformin on insulin sensitivity. Metformin did not affect plasma levels of thyrotropin, free thyroxine, free triiodothyronine, follicle-stimulating hormone, adrenocorticotropic hormone and insulin-like growth factor-1. Conclusions The obtained results suggest that the effect of metformin on overactive lactotropes depends on estrogen levels.

Background Macroprolactinemia is a condition associated with the presence of large amounts of high molecular weight complexes of prolactin. Despite high prevalence, clinical significance of macroprolactin remains poorly understood. Objective The aim of this study was to assess cardiometabolic risk in men with isolated macroprolactinemia. Methods The study population included 11 men with isolated macroprolactinemia, 14 subjects with monomeric hyperprolactinemia and 14 men with prolactin levels within the reference range. Glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine and 25-hydroxyvitamin D were determined in all included patients. Results Compared to healthy counterparts, men with isolated macroprolactinemia had higher levels of 2-h postchallenge glucose, hsCRP and fibrinogen, lower levels of 25-hydroxyvitamin D and reduced insulin sensitivity. Patients with monomeric hyperprolactinemia were characterized by increased plasma levels of 2-h postchallenge glucose, triglycerides, uric acid, hsCRP, fibrinogen and homocysteine, reduced insulin sensitivity and decreased plasma concentrations of HDL cholesterol and 25-hydroxyvitamin D. Subjects with isolated macroprolactinemia differed from patients with monomeric hyperprolactinemia in postchallenge plasma glucose, insulin sensitivity, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D. In men with monomeric hyperprolactinemia, uric acid, hsCRP, fibrinogen, homocysteine and 25-hydroxyvitamin D, while in men with elevated levels of macroprolactin, uric acid, hsCRP, fibrinogen and 25-hydroxyvitamin D correlated with a content of monomeric prolactin or macroprolactin, respectively, as well as with a degree of insulin sensitivity. Conclusions The obtained results suggest that macroprolactinemia may increase cardiometabolic risk but to a lesser extent than monomeric hyperprolactinemia.

Premenopausal women with macroprolactinemia are characterized by increased cardiometabolic risk. No previous study has investigated the impact of any lipid-lowering agent on circulating levels of cardiometabolic risk factors in patients with elevated macroprolactin content. We studied 2 groups of women matched for age, body mass index, plasma lipids, and blood pressure: 12 women with macroprolactinemia and 14 women with prolactin levels within the reference range. Because of coexistent isolated hypercholesterolemia, all subjects were then treated with atorvastatin (20 mg daily). Glucose homeostasis markers, plasma lipids, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before entering the study and 6 months later. The treatment arms differed in baseline values of hsCRP and 25-hydroxyvitamin D, as well as in insulin sensitivity. Atorvastatin decreased total and low-density lipoprotein cholesterol levels stronger in women without than in women with macroprolactinemia. In normoprolactinemic women, atorvastatin decreased circulating levels of uric acid, hsCRP, fibrinogen, homocysteine, and increased concentrations of 25-hydroxyvitamin D, whereas in women with macroprolactinemia the drug decreased levels of hsCRP and homocysteine, as well as impaired insulin sensitivity. Both study groups differed in post-treatment insulin sensitivity and post-treatment values of prolactin before polyethylene glycol precipitation, macroprolactin, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. In conclusion, the obtained results suggest that macroprolactinemia may attenuate cardiometabolic effects of atorvastatin.

What is known and objective Thyroid autoimmune diseases occur much more frequently in women than men. Unfortunately, no previous study has determined whether sex hormones produce any effect on thyroid antibody titres. The primary study aim was to assess whether exogenous testosterone affects thyroid autoimmunity in men with Hashimoto's thyroiditis and low testosterone levels. Methods The study population consisted of 34 euthyroid men with autoimmune thyroiditis and testosterone deficiency. On the basis of patient preference, these patients were either treated with oral testosterone undecanoate (120 mg daily; n = 16) or remained untreated (n = 18). Circulating levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin and total testosterone, as well as serum titres of thyroid peroxidase and thyroglobulin antibodies, were measured at the beginning of the study and 6 months later. The structure parameters of thyroid homeostasis (Jostel's thyrotropin index, SPINA-GT and SPINA-GD) were also calculated. Moreover, semen analyses were performed in eight patients in each group. Results and discussion In testosterone-naive men, serum hormone levels and antibody titres remained at the similar levels throughout the study. Apart from increasing serum testosterone levels, testosterone undecanoate reduced titres of thyroid peroxidase and thyroglobulin antibodies and increased SPINA-GT. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, prolactin and testosterone, Jostel's thyrotropin index, SPINA-GD and semen parameters. Testosterone-induced changes in antibody titres correlated with the effect of treatment on SPINA-GT and with serum testosterone levels. What is new and conclusion This study is the first one to have shown that exogenous testosterone may have a protective effect on thyroid autoimmunity in men with Hashimoto's thyroiditis and testosterone deficiency.

Women with polycystic ovary syndrome (PCOS) are characterized by increased cardiometabolic risk. The aim of the current study was to compare the impact of atorvastatin on plasma levels of cardiometabolic risk factors between men whose sisters had either PCOS or were unaffected.The study population consisted of two age-, fat-free mass index-, blood pressure- and plasma lipid-matched groups of men with elevated total and LDL cholesterol levels: 20 brothers of PCOS probands (group 1) and 20 brothers of healthy women (group 2). Both groups were then treated with atorvastatin (40 mg daily) for the following 6 months. At the beginning and at the end of the study, we assessed plasma lipid levels, glucose homeostasis markers and levels of dehydroepiandrosterone sulfate, testosterone, bioavailable testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and 25-hydroxyvitamin D.At the beginning of the study, both treatment arms differed in the degree of insulin resistance, calculated bioavailable testosterone, as well as in plasma levels of dehydroepiandrosterone sulfate, uric acid, hsCRP and 25-hydroxyvitamin D. Although atorvastatin reduced total and LDL cholesterol levels, this effect was stronger in group 2 than group 1. In group 2, atorvastatin exerted also a more potent impact on hsCRP, fibrinogen and homocysteine. An unfavorable impact on insulin sensitivity was observed only in group 1; while, statistically significant changes in uric acid and 25-hydroxyvitamin D levels were found only in group 2.The obtained results suggest that cardiometabolic effects of atorvastatin are less pronounced in male siblings of PCOS probands than in brothers of unaffected women.

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.

Background In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. Methods The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30 μg) and drospirenone (3 mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Results Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Conclusions Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients.

Background: Low vitamin D status is associated with autoimmune thyroid disease. Oral vitamin D supplementation was found to reduce titers of thyroid antibodies in levothyroxine-treated women with postpartum thyroiditis and low vitamin D status. Methods: The study included 34 women with Hashimoto’s thyroiditis and normal vitamin D status (serum 25-hydroxyvitamin D levels above 30 ng/mL) who had been treated for at least 6 months with levothyroxine. On the basis of patient preference, women were divided into 2 groups, receiving (n=18) or not receiving (n=16) oral vitamin D preparations (2000 IU daily). Serum levels of thyrotropin, free thyroxine, free triiodothyronine and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: There were no significant differences in baseline values between both study groups. 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. No changes in hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers were observed in vitamin-naive patients. Vitamin D increased serum levels of 25-hydroxyvitamin D, as well as reduced titers of thyroid antibodies. This effect was more pronounced for thyroid peroxidase than for thyroglobulin antibodies and correlated with their baseline titers. Conclusions: Vitamin D preparations may reduce thyroid autoimmunity in levothyroxine-treated women with Hashimoto’s thyroiditis and normal vitamin D status.

Background: Metformin as well as dopaminergic agents exert a beneficial effect on glucose and lipid metabolism, often impaired in patients with hyperprolactinemia. Objective: The aim of this study was to compare metabolic- and prolactin-lowering effects of low-dose bromocriptine/metformin combination therapy and cabergoline in patients with elevated prolactin levels. Methods: The study included 27 women with hyperprolactinemia and impaired glucose tolerance who were treated with moderate doses of bromocriptine but experienced adverse effects of this treatment. In 12 of these patients bromocriptine was replaced with cabergoline (group A), while the remaining ones continued treatment with bromocriptine, the dose of which was halved, and administered together with metformin (group B). Plasma lipids, glucose homeostasis markers, as well as serum levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed before and after 4 months of metformin treatment. Results: Both groups did not differ in baseline levels of plasma glucose and lipids, in insulin sensitivity, as well as in circulating levels of all measured hormones. All patients from group A and 12 patients from group B completed the study. Cabergoline reduced prolactin levels, while no effect on plasma prolactin was found in group B. Neither cabergoline nor bromocriptine plus metformin affected circulating levels of thyrotropin and IGF-1. Both treatment options, particularly low-dose bromocriptine plus metformin, improved glucose and lipid homeostasis. Conclusions: Low-dose bromocriptine combined with metformin may be an interesting alternative to cabergoline in patients with mild hyperprolactinemia and early glucose metabolism abnormalities, in whom moderate doses of bromocriptine are poorly tolerated.

Background Vitamin D is suggested to reduce cardiovascular risk. Hypothesis Circulating levels of plasma lipids and other cardiovascular risk factors may differ between statin-treated patients with different vitamin D status. Methods We studied 3 age- and weight-matched groups of men with elevated low-density lipoprotein cholesterol (LDL-C) levels: vitamin D–naive men with vitamin D insufficiency (group A, n = 18), men with vitamin D deficiency/insufficiency effectively treated with vitamin D preparations (group B, n = 16), and vitamin D–naive men with normal vitamin D status (group C, n = 16). All patients were then treated with atorvastatin (20 mg daily) for 4 months. Plasma lipids, glucose homeostasis markers, and plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and at the end of atorvastatin therapy. Results Study groups did not differ in baseline levels of plasma lipids. Men with vitamin D deficiency or insufficiency effectively treated with vitamin D preparations were characterized by decreased insulin sensitivity and higher circulating levels of hsCRP, homocysteine, and fibrinogen in comparison with the remaining groups of patients. Although atorvastatin decreased plasma levels of total cholesterol and LDL-C to a similar extent in all study groups, its effect on uric acid, hsCRP, homocysteine, and fibrinogen was more pronounced in patients from groups B and C than in men from group A. Moreover, in patients with vitamin D insufficiency, atorvastatin impaired insulin sensitivity. Conclusions The obtained results indicate that the strength of pleiotropic effects of atorvastatin depends on vitamin D status.

Atherosclerosis is an inflammatory disease that affects arterial wall. It leads to wall thickening and its instability. As a result a reduction in lumen diameter and blood flow is observed. This manifests predominantly as the affectation of vascular bed of coronary (myocardial infarction), cerebral, carotid (ischemic stroke) or peripheral arteries (limb amputation). One of the most important factors that accelerate atherosclerosis is hyperlipidemia. According to current guidelines the main attention should be focused on the treatment of hyperlipidemia (beside the prevention, which includes proper diet, physical activity and risk factors avoidance). Major attention is given to LDL (low-density lipoprotein) cholesterol (LDL-C) level as primary, and triglyceride level as secondary targets of therapy. As a result of recent clinical findings and continuous research in the field of hypolipidemic drugs it seems practical to review recent data and show potential new pathways that may be useful in the treatment of hyperlipidemia. The review is divided into several parts presenting the widely used and well-known hypolipidemic drugs. In the first part a brief review of contemporary drugs affecting LDL cholesterol is shown. The second part contains information regarding currently available drugs reducing triglycerides level. The third part describes several novel and promising groups of drugs that are still on various steps of clinical development. In the last part drugs affecting HDL (high-density lipoprotein) level were presented.

Background In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin. No previous study has investigated its impact on plasma prolactin in patients with drug-induced hyperprolactinemia. Methods The study included 20 women with antipsychotic-induced hyperprolactinemia and 12 normoprolactinemic women, who, because of coexisting glucose metabolism abnormalities, were treated for 6 months with metformin. Hyperprolactinemic patients with prediabetes received moderate doses of metformin (1.7 g daily), while hyperprolactinemic and normoprolactinemic patients with type 2 diabetes were treated with high-dose metformin (2.55–3 g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, as well as plasma levels of prolactin, thyrotropin, adrenocorticotropic hormone and insulin-like growth factor-1 were assessed at baseline and after 6 months of treatment. Results Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels. No changes in thyrotropin, adrenocorticotropic hormone, and insulin-like growth factor-1 were observed in any treatment groups. Conclusions The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone.

Introduction: Although both statins and fibrates have been found to reduce monocyte cytokine release, no study has investigated whether the effect of hypolipidaemic agents depends on age. Material and methods: This study retrospectively analysed the results of 65 patients with type 2 diabetes and atherogenic dyslipidaemia, complying with lifestyle intervention, and receiving metformin. These patients were then treated with simvastatin (40 mg daily), micronized fenofibrate (200 mg daily), or simvastatin plus fenofibrate. Tumour necrosis factor-alpha (TNF-alpha), inteleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1) release, as well as circulating levels of high-sensitivity C-reactive protein (hsCRP), were determined separately for patients aged between 20 and 50 years and between 51 and 75 years before the study and after 12 weeks of hypolipidaemic treatment. Results: Older adults were characterised by higher monocyte release of TNF-alpha and interleukin-6, as well as higher circulating levels of hsCRP, than the younger subjects. The decrease in monocyte release of all investigated cytokines and in plasma hsCRP was similar in both age groups. In turn, the effect of fenofibrate, alone or in combination with simvastatin, on TNF-alpha, interleukin-6, and hsCRP, but not on interleukin-1beta and MCP-1, was stronger in patients aged between 50 and 75 years, and correlated with an improvement in insulin sensitivity only in this age group. Conclusions: Our results suggest that age may partially determine monocyte-suppressing and systemic anti-inflammatory effects of fenofibrate. (Endokrynol Pol 2016; 67 (2): 190–196)

Background Statins have been found to exert antiinflammatory and immunomodulatory properties. The aim of this study was to compare the effects of intensive and less aggressive statin treatment on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in patients with Hashimoto's thyroiditis. Methods The study included 38 adult women with Hashimoto's thyroiditis, who required statin therapy and were allocated into one of two groups. Patients at very high cardiovascular risk ( n = 16) received intensive statin treatment (rosuvastatin 20–40 mg daily), while patients at moderate or moderately high cardiovascular risk ( n = 22) were treated with simvastatin (20–40 mg daily) for the following 6 months. Serum levels of thyrotropin, total and free thyroid hormones, and high-sensitivity C-reactive protein (hsCRP), as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning and at the end of the study. Results Thirty-six individuals completed the study and were included in the final analyses. Apart from improving plasma lipids and reducing circulating levels of hsCRP, intensive, but not less aggressive, statin therapy reduced thyroid peroxidase and thyroglobulin antibody titers, as well as tended to reduce circulating levels of thyrotropin. The effect of intensive statin therapy on thyroid antibody titers was lipid-independent but correlated with treatment-induced changes in thyrotropin and hsCRP. Conclusions Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are able to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis, intensive statin therapy is required to produce this effect.

Chronic metformin treatment was found to reduce elevated thyrotropin levels. Amiodarone treatment is associated with a range of effects in thyroid function from mild derangements to overt thyroid dysfunction. No previous study has investigated the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with amiodarone-induced hypothyroidism.The study included three age-, sex- and weight-matched groups of amiodarone-treated patients with type 2 diabetes: patients with treated overt hypothyroidism (group I, n=15), patients with untreated subclinical hypothyroidism (group II, n=15), and subjects without thyroid disorders (group III, n=18). The lipid profile, fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin, insulin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 6 months of metformin treatment (2.55-3g daily).In all groups of patients, metformin reduced plasma glucose and triglycerides, serum insulin, glycated hemoglobin as well as HOMA1-IR. The estimated glomerular filtration rate, thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. In patients with untreated amiodarone-induced hypothyroidism, but not in the other groups of patients, metformin reduced serum levels of thyrotropin and this effect correlated weakly with its action on insulin sensitivity.The obtained results indicate that the effect of metformin on hypothalamic-pituitary-thyroid axis activity is partially related to thyroid function. Metformin treatment may bring clinical benefits to patients with amiodarone-induced hypothyroidism and poor tolerance of exogenous L-thyroxine.

GLP-1 agonists such as exenatide and liraglutide are novel drugs for the treatment of diabetes and obesity. While improvements in glycemic control can rely on an incretin effect, the mechanisms behind the loss of weight following therapy have yet to be completely elucidated, and seem to be associated with alterations in eating habits, resulting from changes in cytokines e.g. interleukin 1β (IL-1β) and oxidative signaling in the central nervous system (CNS). Increased levels of IL-1β and reactive oxygen species have been demonstrated to exert anorexigenic properties, and astrocytes appear to actively participate in maintaining the integrity of the CNS, which includes the paracrine secretion of inflammatory cytokines and involvement in the redox status. Therefore, the present study decided to explore the influence of exenatide [a glucagon-like peptide 1 (GLP-1 agonist)] on inflammatory and oxidative stress markers in cultured human astrocytes as a potential target for weight reduction therapies. In an experimental setting, normal human astrocytes were subjected to various glycemic conditions, including 40 mg/dl-hypoglycemic, 100 mg/dl-normoglycemic and 400 mg/dl-hyperglycemic, and exenatide, which is a GLP-1 agonist. The involvement of intracellular signaling by a protein kinase A (PKA) in the action of exenatide was estimated using a specific PKA inhibitor-PKI (14-22). The expression levels of IL-1β, nuclear factor kappa κB (NFκB), glial-fibrillary acidic protein (GFAP), p22 NADPH oxidase, glutathione peroxidase, catalase, superoxide dismutase 1, and reactive oxidative species were measured. The present study demonstrated that varying glucose concentrations in the culture media did not affect the protein expression or the level of reactive oxygen species. Conversely, exenatide led to an increase in IL-1β in normoglycemic culture conditions, which was accompanied by the increased expression of p22, glutathione peroxidase and the reduced expression of GFAP. Changes in the expression of IL-1β and p22 were dependent on the activation of PKA. The present study concluded that exenatide predominantly affected astrocytes in normoglycemic conditions, and hypothesize that this impact demonstrated one of novel mechanisms associated with astrocyte signaling that may contribute to weight loss.

Background Individuals with non-classic congenital adrenal hyperplasia (NC-CAH) often show evidence of hyperandrogenism, including premature pubarche, accelerated linear growth velocity, short final height, hirsutism, acne, alopecia, impaired ovulation, menstrual dysfunction and subfertility. Although statins were found to reduce elevated levels of androgens in subjects with this disorder, no previous study has investigated whether 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors affect cardiometabolic risk factors in patients with NC-CAH. Methods We studied 12 women with NC-CAH, 6 of whom because of coexisting hypercholesterolemia received atorvastatin (20–40 mg daily). Circulating levels of lipids, glucose homeostasis markers, plasma levels of androgens, 17-hydroxyprogesterone, high-sensitivity C-reactive protein (hsCRP), uric acid, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR) were determined at the beginning of the study and 12 weeks later. Results Beyond affecting plasma lipids, atorvastatin reduced circulating levels of testosterone, dehydroepiandrosterone sulphate, androstenedione and 17-hydroxyprogesterone, and decreased free androgen index. Moreover, atorvastatin caused a decrease in plasma levels/urinary loss of uric acid, hsCRP, homocysteine and UACR, and insignificantly increased circulating levels of 25-hydroxyvitamin D. The drug produced no effect on plasma fibrinogen. The effect of atorvastatin on hsCRP, uric acid, homocysteine, 25-hydroxyvitamin D and UACR correlated with the magnitude of reduction in 17-hydroxyprogesterone and androgens. Conclusion Our results suggest that statin therapy reduces cardiometabolic risk in women with NC-CAH.

In many studies, selenium supplementation decreased serum titers of thyroid antibodies. The aim of the study was to investigate whether statin therapy determines selenium action on thyroid autoimmunity.This prospective case-control study enrolled 42 euthyroid women with Hashimoto's thyroiditis and normal vitamin D status, 20 of whom had been treated with atorvastatin (40 mg daily) for at least 6 months. All patients received selenomethionine (200 µg daily) for 6 months. Plasma levels of lipids, serum titers of thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) antibodies, as well as serum levels of thyrotropin, free thyroid hormones, and 25-hydroxyvitamin D were determined at the beginning and at the end of the study.At baseline, there were no differences between both treatment arms in plasma lipids, titers of thyroid antibodies, serum levels of thyrotropin, free thyroid hormones, and 25-hydroxyvitamin D. Selenometionine decreased titers of TPOAb (from 843 ± 228 to 562 ± 189 U/mL) and TgAb (from 795 ± 286 to 501 ± 216 U/mL) in atorvastatin-treated women, as well as titers of TPOAb (from 892 ± 247 to 705 ± 205 U/mL) and TgAb (from 810 ± 301 to 645 ± 224 U/mL) in statin-naive women. The changes in antibody titers were more pronounced in women receiving atorvastatin (between-group difference: 94 [32-156] [TPOAb]; 129 [52-206] [TgAb]). Treatment-induced changes in TPOAb and TgAb correlated positively with baseline thyroid antibody titers. Circulating levels of lipids, free thyroxine, free triiodothyronine, and 25-hydroxyvitamin D remained at similar levels throughout the study.The obtained results indicate that the decrease in titers of thyroid antibodies was potentiated by atorvastatin use.

The need to reduce residual cardiovascular risk led to the development of novel therapeutic strategies to improve patients' outcomes. The residual risk in people with atherogenic dyslipidemia, despite LDL reduction obtained mainly by statins, remains high. Fibrates in those patients lead to significant clinical improvements. Those include reduction in the progression of atherosclerosis, which translates into decrease in cardiovascular events and improvements in microvascular diabetic complications. Furthermore, there are other clinical and biochemical benefits connected with fibrate therapy (e.g. improved insulin sensitivity). Nevertheless, similar to all effective therapeutic modalities, fibrates are associated with unfavorable effects that may lead to complications or treatment discontinuation. Here, we provide up-to-date review of benefits and potential risks associated with the therapy with fibrates. Area covered: A review of available data from clinical trials, meta-analyses and case-reports on the efficacy of fibrate treatment was performed. A specific attention was given to clinical and biochemical benefits as well as adverse events that were reported. Expert commentary: Fibrates are performing well as drugs that reduce residual risk in patients with atherogenic dyslipidemia and hypertriglyceridemia. The adverse events rate is not negligible, but definitely manageable by selection of proper target population and supervision of treated patients.

Both exogenous vitamin D and selenium reduce thyroid antibody titers. The aim of the study was to investigate whether the impact of vitamin D on thyroid autoimmunity is affected by selenium intake. The study included 47 euthyroid women with Hashimoto’s thyroiditis and low vitamin D status, 23 of whom had been treated with selenomethionine (200 μg daily) for at least 12 months before the beginning of the study. During the study, all patients were treated with vitamin D preparations (4000 IU daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D were measured before vitamin D supplementation and 6 months later. Moreover, at the beginning and at the end of the study, we calculated Jostel’s thyrotropin index, the SPINA-GT index and the SPINA-GD index. With the exception of the free triiodothyronine/free thyroxine ratio and the SPINA-GD index, there were no differences between the study groups. In both groups, vitamin D increased 25-hydroxyvitamin D levels, reduced thyroid peroxidase and thyroglobulin antibody titers, as well as increased the SPINA-GT index. The effects on antibody titers and the SPINA-GT index were more pronounced in women receiving selenomethionine. Neither in selenomethionine-treated nor in selenomethionine-naive women vitamin D affected serum hormone levels, Jostel’s index and the SPINA-GD index. The results of the study suggest that selenium intake enhances the effect of vitamin D on thyroid autoimmunity.

Introduction Severe psoriasis is a chronic systemic immune‑mediated disease associated with increased cardiovascular (CV) risk and several comorbidities. Objectives Our aim was to assess vascular indices and selected serum biomarkers of increased CV risk in patients with nonsevere psoriasis. Patients and methods The study group included 80 patients with mild or moderate psoriasis (mean [SD] psoriasis area severity index, 18.6 [10.5]), and the control group included 39 individuals matched forage and body mass index. All patients underwent a comprehensive clinical assessment with aplanation tonometry (pulse wave velocity [PWV]), and the following ultrasound indices were measured: flowmediated dilation (FMD) and carotid intima‑media thickness (IMT). Moreover, the following biomarkers were assessed in all individuals: osteoprotegerin, advanced oxidation protein products (AOPPs), visfatin, and nesfatin. Results Patients with nonsevere psoriasis had increased carotid IMT (mean [SD], 1027 [35] μm vs 587 [12] μm; P0.05), impaired FMD (mean [SD], 16.3% [10.7%] vs 32.1% [13.7%]; P0.001), and increased serum levels of AOPPs (mean [SD], 218.9 [44.6] μmol vs 162.1 [9.9] μmol; P0.001) and visfatin (mean [SD], 13.1 [16.7] ng/ml vs 3.43 [1] ng/ml; P0.001) compared with the control group. There were no significant differences in the serum levels of osteoprotegerin, nesfatin, and PWV. Oxidative stress (AOPP) was significantly associated with IMT (r = 0.3), FMD (r = -0.25), and visfatin (r = 0.6). Conclusions Our study suggests increased CV risk in patients with mild to m oderate psoriasis.

Introduction Severe psoriasis is a chronic systemic immune‑mediated disease associated with increased cardiovascular (CV) risk and several comorbidities. Objectives Our aim was to assess vascular indices and selected serum biomarkers of increased CV risk in patients with nonsevere psoriasis. Patients and methods The study group included 80 patients with mild or moderate psoriasis (mean [SD] psoriasis area severity index, 18.6 [10.5]), and the control group included 39 individuals matched forage and body mass index. All patients underwent a comprehensive clinical assessment with aplanation tonometry (pulse wave velocity [PWV]), and the following ultrasound indices were measured: flowmediated dilation (FMD) and carotid intima‑media thickness (IMT). Moreover, the following biomarkers were assessed in all individuals: osteoprotegerin, advanced oxidation protein products (AOPPs), visfatin, and nesfatin. Results Patients with nonsevere psoriasis had increased carotid IMT (mean [SD], 1027 [35] μm vs 587 [12] μm; P

Long-term prolactin excess is often accompanied by numerous metabolic complications. No previous study has compared the effect of statin therapy on circulating levels of cardiometabolic risk factors in patients with elevated and normal prolactin levels. The study population consisted of 3 age-, weight-, and lipid-matched groups of young women: 19 women with untreated hyperprolactinemia (group A), 20 normoprolactinemic women receiving bromocriptine treatment (because of previous hyperprolactinemia) (group B), and 20 untreated women with prolactin levels within the reference range (group C). Because of elevated total and low-density lipoprotein cholesterol levels, all women were then treated with atorvastatin (40 mg daily). Apart from measuring plasma lipids, glucose homeostasis markers, and hormone levels at the beginning of the study and 12 weeks later, we measured circulating levels of uric acid, high-sensitivity C-reactive protein, homocysteine, and fibrinogen. Despite similar baseline levels of plasma lipids, levels of uric acid, high-sensitivity C-reactive protein, homocysteine, and fibrinogen as well as the degree of insulin resistance were higher in group A than in the remaining 2 groups. Atorvastatin reduced total and low-density lipoprotein cholesterol levels in all study groups. However, only in normoprolactinemic women (groups B and C) did atorvastatin reduce circulating levels of nonlipid cardiometabolic risk factors, whereas only in group A did the drug slightly impair insulin sensitivity. The results of the study suggest that cardiometabolic effects of atorvastatin depend on the prolactin status of patients.

Background Both selenium and vitamin D were found to reduce thyroid antibody titers in women with Hashimoto’s thyroiditis. Methods The study enrolled 37 young drug-naive euthyroid men with autoimmune thyroiditis, who were treated for 6 months with either exogenous vitamin D (group A, n = 20) or selenomethionine (group B, n = 17). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin and free thyroid hormones, serum levels of 25-hydroxyvitamin D, as well Jostel’s thyrotropin, the SPINA-GT and the SPINA-GD indices were determined at the beginning and at the end of the study. Results At baseline, there were no differences between the study groups. Both vitamin D and selenomethionine reduced antibody titers and increased the SPINA-GT index. Only selenomethionine affected the SPINA-GD index, while only vitamin D increased 25-hydroxyvitamin D levels. Neither selenomethionine nor vitamin D significantly affected thyrotropin and free thyroid hormone levels. The effect of vitamin D on antibody titers correlated with baseline and treatment-induced changes in serum levels of 25-hydroxivitamin D. Conclusions Both vitamin D and selenomethionine have a beneficial effect on thyroid autoimmunity in drug-naive men with Hashimoto’s thyroiditis.

Introduction: Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were found to reduce plasma levels of proinflammatory cytokines. No previous study has compared their effect on the production of anti-inflammatory cytokines. Material and methods: The study enrolled 52 patients with grade 1 and grade 2 arterial hypertension. The participants were divided into two groups treated with either perindopril (4 mg daily) or telmisartan (40 mg daily). Blood pressure, plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, interleukins 4, 10, 13 (IL-4, IL-10, IL-13), and high sensitivity C-reactive protein (hsCRP) were measured at the beginning of the study and six weeks later. Results: Both perindopril and telmisartan reduced systolic (SBP) and diastolic blood pressure (DBP). Although both agents increased serum levels of IL-10, this effect was more pronounced in patients treated with telmisartan. Neither telmisartan nor perindopril affected circulating levels of uric acid, glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, IL-4, IL-13, and hsCRP. The effect of telmisartan on IL-10 slightly correlated with an improvement in insulin sensitivity. Treatment-induced changes in IL-10 did not correlate with hypotensive properties of perindopril and telmisartan. Conclusions: The obtained results indicate that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers administered for a short period of time produce a relatively week effect on anti-inflammatory cytokines, limited to IL-10, and stronger for telmisartan than for perindopril.

Postpartum thyroiditis is a form of autoimmune thyroiditis developing during the first 12 months postpartum in 5-10% of women as a consequence of the immunologic flare following the immune suppression of pregnancy. Autoimmune polyendocrine syndromes are rarely diagnosed conditions characterized by the association of at least two organspecific autoimmune disorders, and on the basis of their clinical picture, they may be divided into four different types. The underestimation of their real frequency probable results from physicians’ inadequate knowledge of these clinical entities and sometimes their atypical clinical picture. Although autoimmune thyroid disease may be a component of both type 2 and 3 autoimmune polyendocrine syndromes, but the association between postpartum thyroiditis and autoimmune conditions of other endocrine organs has very rarely been described in literature. We report a case of a young woman, who after two subsequent pregnancies developed postpartum thyroiditis of different clinical pictures. After her second pregnancy, postpartum thyroiditis was followed by the development of autoimmune adrenal failure and premature ovarian failure, which allowed to diagnose type 2 autoimmune polyendocrine syndrome. Our case study suggests that every person with postpartum thyroiditis, particularly if this disorder is accompanied by atypical clinical manifestation, should be assessed for the possible presence of autoimmune polyendocrine syndrome.

Aging is associated with important changes in thyroid hormone secretion, metabolism, and action. It remains unclear, however, whether altered activity of the hypothamic-pituitary- thyroid axis represents physiologic changes in thyroid function or whether they are secondary to thyroid dysfunction. The prevalence of thyroid disorders increases with age, but because some thyroid-associated symptoms are similar to symptoms of the aging process, these disorders are relatively rarely diagnosed. On the other hand, because of the possible presence of chronic, non-thyroidal illnesses or pharmacotherapy, diagnosis of thyroid disorders in older populations is often much more challenging than in young people. Progress made in better understanding of thyroid disorders in older people has thrown a new light on the management of patients with these disorders, the clinical picture of which is often atypical. Therefore, physicians need a high index of suspicion to detect thyroid dysfunction in an older person with multiple comorbidities and chronic polypharmacy. The purpose of this article is to review the present state of knowledge on the age-related changes in hypothalamicpituitary- thyroid axis activity and to discuss the clinical course, diagnosis and treatment of thyroid disorders in the elderly.

Background Metformin was found to decrease serum levels of prolactin and thyrotropin. The aim of this study was to investigate the effect of this drug on hypothalamic-pituitary-ovarian axis activity in postmenopausal women with recently diagnosed and untreated glucose metabolism abnormalities. Methods The study included three matched groups of postmenopausal women: patients with type 2 diabetes (group A, n=16), women with prediabetes (group B, n=14), and individuals with normal glucose metabolism (group C, n=14). Women with diabetes were then treated with high-dose metformin (3 g daily), while women with prediabetes received moderate doses of this agent (1.7 g daily). Glucose homeostasis markers, as well as serum levels of FSH, LH, thyrotropin, prolactin, estradiol and creatinine were measured at baseline and after 16 weeks of metformin treatment. Results In both groups of metformin-treated women, the drug improved glucose homeostasis. High-dose metformin treatment reduced circulating levels of FSH and tended to reduce serum levels of LH, and these effects correlated with an improvement in insulin sensitivity. No changes in gonadotropin levels were observed in prediabetic women receiving moderate doses of metformin. Serum levels of thyrotropin, prolactin and estradiol, as well as the estimated glomerular filtration rate remained at a similar level throughout the study. Conclusions Our study shows that the effect of metformin on hypothalamic-pituitary-ovarian axis activity in postmenopausal women depends on its dose and the magnitude of insulin resistance.

Background By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). Methods The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20–40 mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100 mg weekly, n = 16) and not treated with this hormone ( n = 15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy. Results Compared with the control age-, weight, and lipid-matched statin-naive subjects with LOH ( n = 12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naive patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity. Conclusions Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH.

Our aim was to assess the attainment of primary (low density lipoprotein cholesterol; LDL-C) and secondary (non-high density lipoprotein cholesterol; non-HDL-C) lipid therapeutic goals in relation to obesity, clinical measures of adiposity and ultrasound indexes of fat depots, including the novel index of periarterial adipose tissue (PAT): carotid artery extra media thickness (EMT).High and very high cardiovascular (CV) risk patients (n = 420; F/M: 34/66%; age: 61.2 ± 7 years) with prior statin treatment (≥ 18 months) were enrolled into this cross-sectional study. All patients had a detailed assessment with several anthropometric measures and ultrasound indexes of fat depots indexed to BMI: abdominal (Intra-abdominal Fat Thickness; IAT and Pre-peritoneal Fat Thickness; PreFT), paracardial (Epicardial Fat Thickness; EFT and Pericardial Fat Thickness; PFT) and the new index corresponding to PAT (carotid EMT). Lipid goals attainment in the study group was as follows: 34% (LDL-C goal), 39% (non-HDL-C goal) and 35% (both LDL and non-HDL-C goals). Among ultrasound indexes, patients with both lipid goals attainment revealed significantly lower carotid EMT/BMI (LDL-C goal: 25.2 ± 4.2 vs 27.5 ± 4.1, p0.01 and non-HDL-C goal: 26.1 ± 4 vs 27.7 ± 4.2, p0.01) and IAT/BMI (LDL-C goal: 2.35 ± 0.66 vs 2.51 ± 0.71, p = 0.02 and non-HDL-C goal: p = ns) compared to individuals without goals achievement. Moreover, lipid goals attainment was associated with both measures: carotid EMT/BMI (LDL-C goal: r = -0.2, p0.05 and non-HDL-C goal: r = -0.2, p0.05) and IAT/BMI (LDL-C goal: r = -0.2, p0.05 and non-HDL-C goal: r = -0.2, p0.05). Multivariable regression analysis showed also independent association between carotid EMT/BMI and both goals achievement: LDL-C (p = 0.01) and non-HDL-C goal (p = 0.01). Other fat depots indexes (EFT, PFT and PreFT) failed to provide additional data.Contrary to overall obesity and most clinical measures of adiposity, carotid EMT and abdominal IAT, but not other ultrasound indexes of fat depots revealed associations independent from BMI with lipid goal attainment and may help identify patients requiring more aggressive lipid management.

Background Elevated prolactin levels are associated with metabolic and hormonal complications. No previous study has investigated the effect of any fibrate on plasma levels of lipids and other cardiometabolic risk factors in patients receiving dopamine agonist therapy. Methods The study included 36 premenopausal women with mixed dyslipidemia and slightly increased prolactin levels, 17 of whom had already been treated with bromocriptine (5.0–7.5 mg daily). The included patients received micronized fenofibrate (200 mg daily) for 6 months. Plasma lipids, glucose homeostasis markers, as well as plasma levels of prolactin, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Results Insulin sensitivity was more expressed while baseline plasma levels of hsCRP and fibrinogen were lower in patients treated with bromocriptine than in women not receiving dopamine agonist therapy. Although fenofibrate improved plasma lipids and insulin sensitivity, as well as reduced plasma levels of the investigated cardiometabolic risk factors in both groups of patients, its action on HDL cholesterol, triglycerides, insulin sensitivity, hsCRP and fibrinogen was stronger in subjects receiving bromocriptine. Moreover, only in bromocriptine-naive patients, fenofibrate increased plasma homocysteine. Conclusions Our study shows that the effect of fenofibrate on plasma lipids and circulating levels of cardiometabolic risk factors may be potentiated by bromocriptine treatment. They also suggest that hyperprolactinemic women with mixed dyslipidemia and early glucose metabolism abnormalities may receive the greatest benefits from concomitant treatment with a fibrate and bromocriptine.

Non-classic congenital adrenal hyperplasia (NC-CAH), one of the most common genetic disorders, is often associated with the presence of hyperandrogenism. Recently both simvastatin and metformin were found to reduce plasma steroid hormone levels in this disorder. This study included 8 women with NC-CAH and diabetes or impaired glucose tolerance, as well as 12 matched women with similar glucose metabolism abnormalities but normal adrenal function. Both groups of women, receiving metformin for at least 6 months, were then treated with simvastatin (20 mg daily) for the following 12 weeks. Compared to patients with normal adrenal function, metformin-treated women with NC-CAH showed increased plasma levels of 17-hydroxyprogesterone, total testosterone, free testosterone, androstenedione and DHEA-S. Simvastatin reduced total and LDL cholesterol levels in both patients with NC-CAH and normal adrenal function. Moreover, in the former group of women, statin therapy decreased plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulphate and tended to reduce 17-hydroxyprogesterone. Our results suggest that metformin-statin combination therapy may be useful in the management of symptomatic women with NC-CAH.

Introduction Women with classic forms of congenital adrenal hyperplasia (CAH) or polycystic ovary syndrome have been found to have impaired sexual function. Aim This study investigated sexual activity in young women with nonclassic CAH (NC-CAH). Methods The study included 24 untreated women with NC-CAH and 24 age-matched healthy women. Plasma levels of free and total testosterone, androstenedione, and dehydroepiandrosterone sulfate were measured. Hirsutism was evaluated according to the modified Ferriman-Gallwey score. Questionnaires assessing female sexual function (Female Sexual Function Index) and the presence and severity of depressive symptoms (Beck Depression Inventory, Second Edition) were completed by each participant. Main Outcome Measures Sexual function and depressive symptoms in young women with NC-CAH. Results Women with NC-CAH presented increased plasma levels of 17-hydroxyprogesterone, total and free testosterone, androstenedione, and dehydroepiandrosterone sulfate and higher hirsutism scores compared with healthy women. The study group also showed a lower total Female Sexual Function Index score and lower scores in four domains (sexual arousal, lubrication, sexual satisfaction, and dyspareunia). Scores for sexual desire and orgasm correlated with total hirsutism score and testosterone levels. The Beck Depression Inventory questionnaire showed that the total score was higher in women with NC-CAH than in healthy women, correlating with the hirsutism score and testosterone levels. Conclusion The presence of NC-CAH in young women is associated with impaired sexual function and mild depressive symptoms.

Background Despite a high prevalence of macroprolactinemia in the population, the only drugs found to change macroprolactin (big-big prolactin) levels were dopamine receptor agonists. Methods The aim of this study was to investigate the effect of oral contraceptive pills containing ethinyl estradiol and levonorgestrel on serum macroprolactin levels in patients with macroprolactinemia. The study population included 21 premenopausal women with isolated macroprolactinemia, 11 of whom were treated with oral contraceptive pills. Serum prolactin and macroprolactin levels were assessed at baseline and after 16 weeks of treatment. Results Oral contraceptive pills administered for 16 weeks slightly increased pre-polyethylene glycol serum prolactin levels and macroprolactin levels and the effect of this treatment correlated with their baseline values. Conclusions Our results suggest that oral contraceptive pills containing ethinyl estradiol and levonorgestrel exhibit a stimulatory effect on macroprolactin production in women with basically high macroprolactin levels.

Summary Aims Hyperprolactinemia is often associated with hyperinsulinemia, insulin resistance, atherogenic dyslipidemia, and subclinical atherosclerosis. Dopamine agonists were found to reduce the prevalence of metabolic syndrome and cardiometabolic risk. The aim of this study was to compare the effect of statin therapy on cardiovascular risk factors between patients treated with a dopamine agonist and patients treated with metformin. Methods The study included two age-, weight-, lipid-, and prolactin level-matched groups of premenopausal women with hypecholesterolemia and a history of hyperprolactinemia: patients treated with bromocriptine (5.0–7.5 mg daily, n = 14) and subjects receiving metformin (1.7–2.55 g daily, n = 17). Plasma prolactin, lipids, glucose homeostasis markers, and plasma levels of cardiometabolic risk factors were assessed before and after 12 weeks of atorvastatin treatment. Results Baseline levels of the investigated variables were similar in women treated with bromocriptine and metformin. Apart from lowering total and LDL cholesterol, atorvastatin decreased plasma levels of uric acid, hsCRP, homocysteine, and fibrinogen, with no difference between treatment groups. Conclusions The obtained results suggest that the effect of atorvastatin on plasma lipids and circulating levels of cardiometabolic risk factors does not differ between patients receiving bromocriptine and metformin. Bromocriptine–statin combination therapy may be an alternative to metformin–statin combination therapy in hypercholesterolemic patients with glucose metabolism abnormalities in whom metformin administration is either contraindicated or results in adverse effects.

Introduction: Statins and fibrates reduce monocyte release of proinflammatory cytokines, but it remains unknown whether this effect is sex dependent. Material and methods: We retrospectively analysed age-, weight-, and lipid-matched populations of type 2 diabetic patients of both sexes, who, because of atherogenic dyslipidaemia, were treated with simvastatin (40 mg daily), fenofibrate (200 mg daily), or simvastatin plus fenofibrate. Monocyte release of tumour necrosis factor alpha (TNF-alpha), inteleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1), as well as circulating levels of high-sensitivity C-reactive protein (hsCRP) and free fatty acids (FFA) were assessed separately for men and women before and after 12 weeks of treatment. Results: Baseline monocyte release of TNF-alpha, interleukin-1beta, interleukin-6, and MCP-1, as well as plasma hsCRP and FFA levels were comparable in both sexes. Simvastatin, fenofibrate, and simvastatin/fenofibrate combination therapy reduced monocyte release of TNF-alpha, inteleukin-1beta, interleukin-6, and MCP-1, with no difference between the treatment groups. The impact of simvastatin and fenofibrate administered alone on monocyte cytokine release and systemic inflammation did not differ between the men and women. The effect of simvastatin/fenofibrate combination therapy on monocyte release of interleukin-6 and MCP-1 was more pronounced in the male population. The impact of simvastatin administered together with fenofibrate on TNF-alpha, interleukin-1beta, and hsCRP was also stronger in the men than in the women, but the difference did not reach the level of significance. Conclusions: The obtained results suggest that sex differences determine the strength of the monocyte-suppressing effect of simvastatin/ /fenofibrate combination therapy in type 2 diabetic patients with atherogenic dyslipidaemia. (Endokrynol Pol 2015; 66 (3): 224–230)

Komórki mikrogleju są reprezentantami układu immunologicznego w ośrodkowym układzie nerwowym (OUN). Od dawna były postrzegane jako główny agresor, indukujący i podtrzymujący procesy zapalne i neurodegeneracyjne w OUN. Ostatnie doniesienia naukowe wskazują jednak, że mogą one pełnić istotną rolę ochronną. W niniejszej pracy przedstawiono dowody naukowe, podkreślające ich właściwości przeciwzapalne. Komórki mikrogleju podlegają aktywacji na dwa różne sposoby, co powoduje powstanie dwóch odmiennych fenotypów: klasycznego zapalnego oraz alternatywnego przeciwzapalnego. Ten ostatni charakteryzuje się m.in. ekspresją CD200 oraz fraktalkiny. Alternatywnie aktywowany mikroglej produkuje również cytokiny prozapalne, których wpływ na otaczające komórki nie do końca wiąże się tylko z ich destrukcją, lecz także niejednokrotnie z procesami neuroregeneracji i mielinizacji. Być może przedstawienie najnowszych doniesień skieruje uwagę badaczy na nowe narzędzia mogące znaleźć zastosowanie w zapobieganiu i leczeniu chorób OUN poprzez wykorzystanie przeciwzapalnych właściwości komórek, które wciąż uważa się za komórki prozapalne.

Cinacalcet increases calcium-sensing receptor (CaSR) sensitivity to serum calcium. CaSR is expressed by adipocytes, and adiponectin is an adipokine with antiatherogenic and insulin-sensitizing properties. The aim of this study was to assess the influence of a 3-month cinacalcet regimen on plasma adiponectin concentration in hemodialyzed patients (HDP) with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT).Plasma adiponectin, advanced oxidation protein products (AOPP), serum interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations were assessed in 65 HDP with sHPT treated with cinacalcet (30-120 mg/day) before the first dose and after 3 months of treatment.There was a significant decrease in serum parathyroid hormone (PTH) concentration: from 1,089 (891-1,286) pg/mL to 775 (574-976) pg/mL after 3 months of treatment (P.0001). The treatment was associated with a significant (P = .048) increase in plasma adiponectin concentration from 16.9 (14.4-19.5) μg/mL to 17.8 (15.0-20.6) μg/mL. Significant (P = .03) reduction of plasma AOPP concentration was observed from 186.7 (156.7-216.7) pg/mL to 162.6 (141.2-183.9) pg/mL.A 3-month cinacalcet regimen increased plasma adiponectin concentrations in HDP with sHPT. Increased adiponectinemia in these patients may be related to reduced oxidative stress.

Macrophages are dominant cells in the pathogenesis of atherosclerosis. They are also a major source of reactive oxygen species (ROS). Oxidative stress, which is particularly high in subjects with diabetes, is responsible for accelerated atherosclerosis. Novel antidiabetic drugs (e.g., glucagon-like peptide-1 (GLP-1) agonists) were shown to reduce ROS level. Therefore, we conceived a study to evaluate the influence of exenatide, a GLP-1 agonist, on redox status in human monocytes/macrophages cultured in vitro, which may explain the beneficial effects of incretin-based antidiabetic treatment. Human macrophages obtained from 10 healthy volunteers were in vitro subjected to the treatment with GLP-1 agonist (exenatide) in the presence of lipopolysaccharide (LPS), antagonist of GLP-1 receptors (exendin 9-39), or protein kinase A inhibitor (H89). Afterwards, reactive oxygen species, malondialdehyde level, NADPH oxidase, and antioxidative enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase] expression was evaluated. Finally, we estimated the activity of the abovementioned enzymes in the presence of H89. According to our findings, exenatide reduced ROS and malondialdyhyde (MDA) level by decreasing the expression of ROS-generating NADPH oxidase and by increasing the expression and activities of SOD and GSH-Px. We also showed that this effect was significantly inhibited by exendin 9-39 (a GLP-1 antagonist) and blocked by H89. Exenatide improved the antioxidative potential and reduced oxidative stress in cultured human monocytes/macrophages, and this finding may be responsible for the pleiotropic effects of incretin-based therapies. This effect relied on the stimulation of GLP-1 receptor.

HERV-W is a multi-locus family of human endogenous retroviruses (HERVs) that has been found to play an important role in human physiology and pathology. Two particular members of HERV-W family are of special interests: ERVWE1 (coding syncytin-1, which is a glycoprotein essential in the formation of the placenta) and MSRV (multiple sclerosis-associated retrovirus that is thought to play a significant role in human pathology as a result of its increased expression in the brain tissue and blood cells derived from patients with multiple sclerosis (MS)). Both ERVWE1 and MSRV mRNA share high level of similarity and hence a method that allows to exclusively quantify the MSRV expression in clinical samples would be desirable. We developed a quantitative polymerase chain reaction (QPCR) technique for the detection and quantification of the multiple sclerosis-associated retrovirus. The assay utilises fluorescently labelled oligonucleotide probe, which is complementary to the conservative fragment of MSRV env gene and a peptide nucleic acid (PNA) probe, fully complementary to the ERVWE1 sequence fragment that efficiently blocks the polymerase action on ERVWE1 templates. The PNA molecule, if used parallel with hydrolysis probe in QPCR analysis, greatly facilitates the detection efficiency of MSRV even if ERVWE1 is present abundantly in respect to MSRV in the analysed sample. We achieved a wide and measurable range from 1 × 10 e(2) to 1 × 10 e(8) copies/reaction; the linearity of the technique was maintained even at the low MSRV level of 1% in respect to ERVWE1. Using our newly developed method we confirmed that the expression of MSRV takes place in normal human astrocytes and in human umbilical vein endothelial cells in vitro. We also found that the stimulation of human monocytes did not influence the specific expression of MSRV but it caused changes in mRNA level of distinct HERV-W templates.

Introduction: Hypolipidaemic agents were found to affect plasma adipokine levels, but no previous study has investigated whether this effect is sex-dependent. Material and methods: We retrospectively analysed 61 patients participating in our previous studies, who because of isolated hypercholesterolaemia were treated with simvastatin (40 mg daily), ezetimibe (10 mg daily) or simvastatin (40 mg daily) plus ezetimibe (10 mg daily). Plasma levels of leptin, adiponectin, visfatin, tumour necrosis factor-alpha (TNF-alpha), free fatty acids (FFA), and high-sensitivity C-reactive protein (hsCRP) were assessed separately for men and women before and after 30 days of treatment. Results: At baseline, plasma levels of adiponectin and leptin were lower, while plasma levels of TNF-alpha were higher in men than in women. Administration of simvastatin and statin/ezetimibe combination for 30 days reduced plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-alpha but increased plasma levels of adiponectin, while the effect of ezetimibe was much more limited. The effect of simvastatin and ezetimibe, administered alone or in combination, on plasma hsCRP, FFA, leptin, adiponectin, visfatin, and TNF-alpha did not differ between men and women. Irrespectively of sex, the changes in plasma adipokines and systemic-anti-inflammatory effects were more expressed in simvastatin — than in ezetimibe-treated patients and were strongest when both these agents were administered together. Conclusions: Our results show that sex differences do not determine the effect of hypolipidaemic agents on adipose tissue and low-grade inflammation. (Endokrynol Pol 2015; 66 (2): 114–120)