Impaired insulin action, frequently found in essential hypertension (HT), is modified by other factors, such as higher age, accumulation of body fat, dyslipidaemia, impaired glucose metabolism and endothelial dysfunction. In addition, antihypertensive and insulin-sensitizing medication itself may significantly affect cardiovascular and metabolic milieu. The aim of this study was to assess insulin sensitivity, acute insulin response, lipidaemic status and the adipokines' concentrations with regard to abdominal fat distribution in young, lean male subjects with treatment-naïve essential HT and in matched healthy normotensive (NT) subjects. We studied 27 HT patients (age: 19.9+/-0.6 years; body mass index (BMI): 22.9+/-0.5 kg m(-2)) and 15 NT controls (age: 22.3+/-1.0 years; BMI: 23.7+/-0.6 kg m(-2)). The subjects underwent an oral and an intravenous glucose tolerance test (OGTT, IVGTT) on separate days in random order. Higher fasting insulin (P<0.001), non-esterified fatty acids (P<0.05) and plasminogen activator inhibitor factor 1 concentrations (P<0.05) were found in HT patients when compared with NT patients. Despite comparable anthropometric parameters and body fat distribution assessed by magnetic resonance imaging in both groups, newly diagnosed untreated young hypertensive male subjects showed decreased insulin sensitivity, augmented insulin response to both oral and intravenous glucose load (P<0.01; P<0.05 respectively) and 'higher still normal' 2-h plasma glucose levels during OGTT. Untreated, young, lean hypertensive male subjects, with distribution of abdominal adipose tissue and lipid profile comparable with their healthy NT matched counterparts, showed considerable signs of insulin resistance and hyperinsulinaemia. We hypothesize that insulin resistance is the initial feature, which is influenced by several environmental factors, and HT is one of their common consequences.Journal of Human Hypertension advance online publication, 15 July 2010; doi:10.1038/jhh.2010.72.

The concept of relative adrenal insufficiency (RAI) has been originally introduced to describe a situation in which critically ill patients, without any prior risk or evidence for adrenal insufficiency, have total serum cortisol levels inadequate for the severity of patients' illness. The concept provided a framework for other disease states, in which higher than normal adrenal function could be expected, such as in chronic inflammation. An intense research in RAI field highlighted some new methodological aspects that significantly improved assessment of adrenal function in chronic illness. Measurement of salivary cortisol may provide additional information on locally available cortisol in target tissues. Low levels of dehydroepiandrosterone (DHEAS) for given age and gender were confirmed as a simple and reliable indicator of decreased adrenal function, even in subjects with normal baseline cortisol or normal corticotropin-stimulated cortisol response. Combined lower DHEAS and lower baseline cortisol levels could be an example of hypocompetence of adrenocortical function, yet clinically not apparent.

The article summarizes reports on the concurrence of Klinefelter's syndrome (KS) with inflammatory rheumatic diseases, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, the antiphospholipid syndrome, and ankylosing spondylitis. These include two case reports of patients with KS concurrently associated with RA or antisynthetase syndrome, respectively, previously reported by the author and his coworkers. Attention is paid to the pathogenesis and the course of the disease in patients with KS. The importance of early diagnosis of the syndrome, when occurring simultaneously with other diseases of connective tissue, is emphasized.

OBJECTIVES: To compare free plasma cortisol (FPC) with salivary and calculated cortisol. DESIGN AND METHODS: FPC, salivary cortisol, free cortisol index (FCI), albumin-derived free cortisol index (FCIalb), Coolen's and Dorin's cortisol were assayed during repeated low-dose ACTH test in healthy women. RESULTS: FPC significantly correlated with its surrogates, the most with FCIalb and salivary cortisol. FPC and salivary cortisol showed the highest method agreement. CONCLUSIONS: FCIalb and salivary cortisol are preferred surrogates of FPC.

OBJECTIVES: Because of well known association between the exposure to persistent organochlorinated pollutants (POPs) and impaired immune system, it was attempted to check possible coincidence of nuclear and thyroperoxidase antibodies with the levels of major POPs. METHODS: Antinuclear antibodies.(ANA) were estimated by indirect immunofluorescence test using Hep2- cells and thyroperoxidase antibodies (TPOab) by electrochemiluminiscent immunoassay in the cohort of 253 adults (82 males and 171 females) aged 21-75 years, among them 144 (46 males and 98 females) from the area polluted (POLL) by polychlorinated biphenyls (PCB) and 109 (36 males and 73 females) from the area of background pollutrion (BCGR). In the same cohort fifteen congeners of PCB and also total DDE (2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene) and hexachlorobenzene (HCB) were estimated by high resolution gas chromatography/mass spectrometry. RESULTS: Prevalence of ANA only was significantly higher in POLL than in BCGR in males (p < 0.001) and females (p < 0.001) and the same was true for the prevalence of TPOab in males (p < 0.05) and females (p < 0.01) from POLL. In addition, also the prevalence of coincident ANA+TPOab in males (p < 0.001) and females (p < 0.05) was significantly higher in POLL. In a total of 253 pooled males and females from both areas and stratified in terms of PCB level quintiles. The prevalence of ANA in the 4th and 5th quintile of each among three pollutants (PCB, DDE and HCB) was significantly higher (p < 0.01 or < 0.001) and showed the parallel increase with the level of all pollutants. CONCLUSIONS: Significantly increased prevalence of ANA either only or in coincidence with TPOab was found related to increasing level of PCB, DDE and HCB.

OBJECTIVE: Clinical and experimental data indicate the involvement of adrenal steroids in the complex of rheumatoid arthritis (RA) pathogenesis. A subtle adrenocortical hypocompetence has been suggested in a subset of glucocorticoid-naïve premenopausal females with RA. METHODS: The interrelations among adrenal steroids: cortisol (CORT), 17alpha-hydroxyprogesterone (17-OHP), androstenedione (ASD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were evaluated in 15 glucocorticoid-naïve premenopausal females with RA and in 14 age- and body mass index- matched healthy females at basal and during insulin-induced hypoglycemia states. Spearman's correlations were used to analyze baseline plasma concentrations as well as areas under response curves of these steroids levels as assayed during the basal and/or insulin-induced hypoglycemia status. RESULTS: Six among 15 RA patients, but none of 14 controls had combined "lower" quartile range of basal cortisol (< 431 nmol/l) and lower DHEAS (< 2.79 micromol/l) levels, i.e., concentrations within the lowest quartiles of the control group (p = 0.017). In all subjects combined, basal correlations were significantly positive between ASD and other steroids (CORT, 17OHP, DHEA, DHEAS). When patient and control groups were analyzed separately, the positive basal correlation between ASD and CORT was significant only in RA patients (p = 0.030). In contrast, a positive basal correlation between ASD and DHEA was significant only in controls (p = 0.004). When comparing the areas under response curves (AUCs), the correlation of ASD and CORT was significantly negative in RA (p = 0.009), but positive in controls (RA vs control difference in Spearman's correlations, p = 0.002). The correlation between AUCs of ASD and DHEA was strongly positive in controls (p = 0.006), but not in RA (RA vs. control difference p = 0.044). CONCLUSIONS: The results suggest relative hypocompetence of adrenocortical function in premenopausal RA females. Different patterns of correlations of the adrenal steroids during basal vs. stimulatory testing suggested certain alterations in adrenal synthetic pathways or deficiencies in the dynamics of steroidogenesis in RA.

Background: The results of low-dose ACTH testing may be impaired during endogenous or exogenous hypercortisolemia in various clinical situations. Aim: The hypothesized inhibitory effects of hypercortisolemia on adrenal responsiveness to low-dose ACTH were tested in two model situations in healthy humans. Subjects and Methods: Nine young healthy women underwent low-dose ACTH test in 5 modifications. In ACTH-ACTH test, ACTH (Synacthen, 1mu i.v.) was given at 09:00 h and 10:00 h. Two control tests consisted of single ACTH bolus at 09:00 h or at 10:00 h. In HCACTH test, hydrocortisone (HC, 20mg orally) was given at 08:30 h and ACTH was injected at 10:00 h. Control test consisted of single HC administration at 08:30 h. Results: Cortisol response after the 2nd ACTH test was significantly lower vs. the 1st ACTH bolus (deltamax: 166+/-32 nmol/l vs. 276+/-15 nmol/l, p<0.05) in ACTH-ACTH test. Responses of other steroids after both ACTH injections were comparable. ACTH bolus during HC-induced hypercortisolemia caused a slight increase in cortisol level and prevented its decrease, seen after HC administration alone. Adrenal cortisol production in response to ACTH bolus under different incipient conditions (baseline, physiological and pharmacological hypercortisolemia; 180+/-16, 173+/-21, and 177+/-53 nmol x min x l-1, respectively) did not significantly differ (p=0.8). Conclusions: Endogenous and exogenous hypercortisolemia did not influence adrenal cortisol response to low-dose ACTH test indicating lack of its negative feedback at adrenal level.

This case report describes successful treatment of autoimmune autonomic ganglionopathy (AAG) in a 74-year-old woman by total plasma exchanges (PLEX) and rituximab. Two series of PLEX temporarily, but dramatically improved orthostatic intolerance and hypotension and baroreflex function, in a manner inversely related to ganglionic neuronal nicotinic receptor antibody titer. After rituximab treatment, the antibody titer was decreased modestly but persistently, and the patient had symptomatic and clinical laboratory evidence of continued benefit for at least 10 months, supporting the autoimmune pathogenesis of AAG.

ABSTRACT: BACKGROUND: Several our previous studies showed associations of increasing blood level of persistent organochlorinated pollutants (POPs) with individual thyroid and metabolic adverse health signs in subjects from heavily polluted area (POLL) compared to these from the area of background pollution (BCGR). In this study we present increasing number of subjects with multiple adverse signs positively associated with blood level of polychlorinated biphenyls (PCBs) which is used as a marker of other POPs cocktail. METHODS: In a total of 2046 adults (834 males and 1212 females; age range 21-75) from POLL and BCGR the serum level of major POPs such as of 15 most abundant PCBs congeners, dichlorodiphenyl-dichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) was estimated by high resolution gas chromatography. In addition, the data on thyroid volume by ultrasound and body mass index were obtained and serum level of thyroperoxidase and thyrotropin receptor antibodies as well as that of free thyroxine, total triiodothyronine, thyrotropin, thyroglobulin, fasting glucose and insulin, cholesterol and triglycerides was measured. Thus, a total of 13 adverse signs were defined and the interrelations between PCBs level and increasing number of subjects with increasing number of adverse signs were evaluated. RESULTS: Because of high correlation between major POPs (PCB, DDE and HCB), for this purpose the level of PCBs was considered as a marker also for the presence of DDE and HCB. Thus, if all data obtained from 2046 subjects were stratified according to quintiles of PCBs level, highly significant increase was found (p<0.02 to 0.0000 by chi-sqauare) for the frequency of 8 among 13 signs, while the increase of one additional sign was slightly above significance limit and that in 4 other was not significant. Also the number of subjects with multiple adverse signs was significantly higher in POLL than in BCGR. For instance, in BCGR area (1038 subjects; median PCB level of 744 ng/g and 5 %-95 % range of 423 - 1329 ng/g serum lipids) there were 84 (8.1 %) cases with 6 or 7 adverse health signs, while in POLL area (1008 subjects; median PCB level of 1892 ng/g; 5 %-95 % range of 685 - 9016 ng/g) the prevalence of respective cases was twice as high (195 cases = 19.3 %; p<0.001 by chi-square). For the subjects with the same PCB levels, but with 8 or 9 adverse signs the respective values were 22/1038 (2.1 %) vs. 54/1008 (5.3 %; p<0.001). CONCLUSIONS: Significantly higher accumulation of adverse signs in subjects with high POPs level was found in POLL thus supporting the conclusion that POPs appear to increase the prevalence of several subclinical and overt thyroid and metabolic disorders.

Several forms of chronic autonomic failure manifest as neurogenic orthostatic hypotension, including autoimmune autonomic ganglionopathy (AAG) and pure autonomic failure (PAF). AAG and PAF are thought to differ in pathogenesis, AAG reflecting decreased ganglionic neurotransmission due to circulating antibodies to the neuronal nicotinic receptor and PAF being a Lewy body disease with prominent loss of sympathetic noradrenergic nerves. AAG therefore would be expected to differ from PAF in terms of clinical laboratory findings indicating post-ganglionic noradrenergic denervation. Both diseases are rare. Here we report preliminary observations about clinical physiologic, neuropharmacologic, neurochemical, and neuroimaging data that seem to fit with the hypothesized pathogenetic difference between AAG and PAF. Patients with either condition have evidence of baroreflex-sympathoneural and baroreflex-cardiovagal failure. Both disorders feature low plasma levels of catecholamines during supine rest, but plasma levels of the other endogenous catechols, dihydroxyphenylalanine (DOPA), dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylglycol (DHPG), seem to be lower in PAF than in AAG, probably reflecting decreased norepinephrine synthesis and turnover in PAF, due to diffuse sympathetic noradrenergic denervation. PAF entails cardiac sympathetic denervation, whereas cardiac sympathetic neuroimaging by thoracic 6-[(18)F]fluorodopamine scanning indicates intact myocardial sympathetic innervation in AAG.