Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoid resistance results from the partial, albeit apparently generalized, inability of glucocorticoids to exert their effects on target tissues. The condition is associated with compensatory increases in circulating pituitary corticotropin and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from chronic fatigue (perhaps a result of glucocorticoid deficiency in the central nervous system) to various degrees of hypertension with or without hypokalemic alkalosis or hyperandrogenism, or both, caused by increased cortisol and other salt-retaining steroids and adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility and in children, to precocious puberty. Different molecular defects, such as point mutations or a microdeletion of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and appear to cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by the overall degree of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor, with selective resistance of certain glucocorticoid responses in specific tissues. The various different symptoms of classic glucocorticoid resistance and the theoretical potential of this condition to appear surreptitiously emphasize the importance of the glucocorticoid receptor in the pathogenesis of human disease.
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PMID:Syndromes of glucocorticoid resistance. 818 39

This review is focused on the diagnostic, clinical and therapeutic aspects of insulin resistance relevant to the clinician. The observed phenomenon of the wide variability of insulin sensitivity in clinically healthy subjects is discussed; qualitative and quantitative aspects of the methodologies currently used for the assessment of insulin sensitivity in the clinical setting are dealt with, as well as their applicability to day-to-day clinical care. The medical consequences of hyperinsulinemia, including dyslipidemia, hypertension coronary artery disease and ovarian hyperandrogenism are likewise discussed. A panoramic view of the various clinical presentations of insulin resistance is also offered, including clinical elements for suspicion, as well as an account of the prevalent, less-prevalent and rare disorders harboring the phenomenon of insulin resistance. The final topic of the review is a novel discussion on the therapeutic possibilities in insulin resistance disorders, including treatment with hormones and antihormones.
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PMID:[Insulin resistance: a frequent phenomenon in clinical practice]. 830 17

Insulin resistance confers increased susceptibility to NIDDM, atherosclerotic cardiovascular disease, ovarian hyperandrogenism, and possibly hypertension. Insulin resistance is largely inherited, in rare cases as a monogenic disorder or more commonly as a complex trait. The search for insulin resistance genes relies mainly on two complementary approaches: 1) positional cloning using random DNA markers present throughout the genome; and 2) the analysis of specific candidate genes. This report briefly summarizes the candidate gene approach to insulin resistance. Progress related to the analysis of genes encoding molecules that participate in insulin action is reviewed. In addition, the spectrum of potential genetic defects that might contribute to insulin resistance, both at the level of the target cell and secondarily (e.g., obesity genes), is discussed.
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PMID:Candidate genes for insulin resistance. 872 72

There exists a growing body of evidence in women that links androgen excess to increases in cardiovascular disease and reproductive site neoplasia. Ten to fifteen percent of women exhibit clinical signs and symptoms of hyperandrogenism wherein more extensive evaluation is warranted. Women with adult acne, android-type obesity, and alopecia often have been treated for cosmetic reasons without regard to the underlying pathophysiology. Adverse changes in insulin resistance, lipids, and apoproteins favor earlier progression of diabetes for some patients and an unfavorable cardiovascular risk profile for most. Patients with polycystic ovarian syndrome (PCOS) often present to different health providers with different complaints that include excessive facial hair, obesity, hypertension, impaired glucose tolerance, dysfunctional uterine bleeding, or infertility. First-line treatment options, after excluding ovarian or adrenal tumors, include use of non-androgenic OCs until pregnancy is desired. Early identification of patients allows for use of risk-reduction strategies, which may affect clinical outcomes.
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PMID:Androgen excess in women. 882 97

Adrenal masses are more and more frequently detected by adrenal ultrasound, computed tomography or nuclear magnetic resonance carried out for a reason other than the suspicion of adrenal disease (incidentalomas). The findings of an incidentaloma still leaves many diagnostic and therapeutic questions open. We report the results of a multicentric retrospective evaluation of patients with adrenal incidentalomas, performed by a Study Group of the Italian Society of Endocrinology. According to the definition of incidentaloma, exclusion criteria a priori were: severe or paroxysmal hypertension, frank hypokalemia and clinical signs of hypercortisolism or hyperandrogenism. 29 centers participated in the study and the data obtained by questionnaire were collected in 2 centers for final elaboration. Center 1 carried out the epidemiological and clinical evaluation. Basal and dynamic hormonal evaluation of 786 among the 1013 cases recruited were performed in our center (center 2). Functional studies included: diurnal rhythm of cortisol, urinary free cortisol (UFC), ACTH, DHEAS, 17-OH progesterone, testosterone, androstenedione, supine and upright plasma renin activity (PRA) and aldosterone, urinary aldosterone, urinary catecholamines and VMA. The hormonal dynamic evaluation included the overnight dexamethasone suppression test (1 mg), CRH test and ACTH test. In our study, 89% (702 patients) of adrenal incidentalomas were non-hypersecretory masses; 6.2% (49 patients) showed a preclinical Cushing's syndrome (PCS) (at least two altered parameters of pituitary-adrenal axis); 3.4% (27 patients) were pheochromocytomas; 0.89% (7 patients) were aldosteronomas. One tumor was a masculinizing adrenocortical carcinoma. Two hundred sixty patients underwent surgical exploration and the histological diagnosis showed: 138 adenomas (53%), 32 carcinomas (12%), 26 pheochromocytomas (10%). 16 myelolipomas (8%), 13 cystic lesions (5.5%), 7 tumors of neuronal lineage (3%). 12 metastases (4%), 13 others (5%). The 138 patients with adenomas had the following hormonal diagnosis: 103 nonfunctional adenomas (74%), 31 PCS (23%) and 4 cases of hyperaldosteronism (3%). In the patients with PCS an abnormal dexamethasone suppression test was found in 86% of cases (37/41 patients). Values for ACTH were low in 78% (32/41 patients). UFC was elevated in 64% of patients, the diurnal rhythm of cortisol evaluated in 14 patients was absent in 7. Only in 50% of cases DHEAS values (12/24 patients) were decreased, whereas they were normal in the other 50%. Interestingly, 8 patients with normal DHEAS and normal UFC showed nonsuppressible cortisol by dexamethasone test (1 mg). Blunted ACTH response to CRH was detected in 9 of 14 patients (64%). Thus our data suggest that the best parameter for evaluating subclinical hypercortisolism seems to be the overnight dexamethasone suppression test. In 27 patients with pheochromocytoma 24-hour urinary catecholamine and VMA levels were elevated in 86 and 46% of cases respectively. In 7 patients with hyperaldosteronism upright PRA was suppressed in 100% of cases and aldosterone plasma levels were elevated in 6 patients (86%); serum potassium level was slightly decreased in 60% of cases. In 86 of 138 histologically proven adenomas, DHEAS levels were: normal in 59% of patients, decreased in 36% and elevated in 4.6%, whereas in 22 of 32 cortical carcinomas evaluated. DHEAS levels were normal in 63% of cases, decreased in 18% and elevated 18%. Post-ACTH 17-OH progesterone levels were elevated in 52% (62/118 patients) of non-functioning adenomas and in 2 of 4 carcinomas. Not enough data are yet available postoperatively. In summary, endocrine evaluation can lead to the identification of a nonnegligible number of cases of clinically unsuspected pheochromocytomas and subtle hypercortisolism (about 3.4 and 6.2%, respectively of all adrenal incidentalomas), while cases of primary subclinical aldosteronism are rarely found. (ABSTRACT TRUNCATED)
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PMID:Adrenal incidentaloma: an overview of hormonal data from the National Italian Study Group. 916 66

Hypertension is often accompanied by a host of metabolic defects. Investigations have shown an association between insulin resistance, hyperinsulinemia, central/visceral obesity, and hypertension. Recent interest has focused on the fact that untreated hypertensive individuals have compensatory hyperinsulinemia, are resistant to insulin-mediated glucose uptake, and frequently have coexisting lipid abnormalities. Data from prospective studies appear to indicate that fasting hyperinsulinemia is an independent predictor of coronary artery disease. Additionally, there is evidence that hyperinsulinemia and diabetes eliminate the normal sex differences in the prevalence of coronary artery disease. The salutary effects of ovarian hormones on the prevalence of hypertension and cardiovascular disease in postmenopausal women are well established. Hyperandrogenism, in particular elevated serum levels of dehydroepiandrosterone sulfate, is believed to be a risk factor promoting sex-specific impairments of glucose and lipid metabolism, obesity, and hypertension in women. Clinical and epidemiologic evidence have linked elevated blood pressure to disturbances in lipoprotein metabolism, fibrinolytic activity, plasminogen activation inhibitor levels, and dyslipidemia. This review briefly presents the current understanding of various metabolic disturbances associated with hypertension, the pathophysiologic mechanisms involved, and the significance of the interplay between them relative to the complications of this disease.
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PMID:Metabolic abnormalities in hypertension. 926 63

Hyperinsulinaemia is found in 30% of slim and 75% of obese women with polycystic ovary syndrome. Despite resistance to insulin action in terms of glucose transport, increased insulin levels may cause hyperandrogenaemia by enhancement of androgen production in the ovaries where insulin acts as co-gonadotrophin. Recent interest in insulin resistance results from the recognition that it predisposes to various metabolic abnormalities, and could be involved in the pathogenesis of atherosclerosis. Women with polycystic ovary syndrome frequently have metabolic disturbances associated with insulin resistance, and recent long-term follow-up studies have indicated that they also have a higher incidence of diabetes and hypertension later in life compared with control populations. This review describes the association of hyperinsulinaemia with hyperandrogenism, metabolic and circulatory changes in women with polycystic ovary syndrome. Special emphasis is placed on recent studies of molecular mechanisms of insulin resistance in polycystic ovary syndrome and clinical implications of hyperinsulinaemia in these women.
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PMID:Insulin resistance in polycystic ovary syndrome. 926 4

Steroid 11 beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol. Severely affected patients carry mutations in the CYB11B1 gene that destroy enzymatic activity. Such patients have signs of androgen excess and usually have hypertension. Mild or non-classic 11 beta-hydroxylase deficiency has been reported previously but not studied genetically. In this study we report analysis of the CYP11B1 genes of three patients thought to suffer from non-classic 11 beta-hydroxylase deficiency. Mutations were detected in the CYP11B1 genes of two patients. One was a compound heterozygote for missense mutations N133H and T319M, whereas the other carried a nonsense mutation (Y423X) on one allele and a missense mutation (P42S) on the other. All three missense mutations affected enzymatic activity when expressed in vitro. No mutations were detected in the coding regions or intron-exon boundaries of the CYP11B1 genes of the other putative non-classic patient. In addition, we were unable to detect CYP11B1 mutations in two hirsute women with mildly elevated levels of 11 beta-hydroxylase precursors who had previously been identified in a screening study of patients in a reproductive endocrinology clinic. We conclude that nonclassic 11 beta-hydroxylase deficiency is a rare disorder. It is not a significant cause of hyperandrogenism in women and relatively stringent criteria should be used to prevent its misdiagnosis.
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PMID:CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. 930 60

About 30% of infertility is caused by anovulation, associated most commonly with the polycystic ovary syndrome (PCOS). PCOS is a common endocrinopathy in women, especially at the age of 30 to 35 years, characterized by irregular menses, infertility and signs of hyperandrogenism. The pathogenetic mechanisms leading to PCOS are not fully understood, although several theories have been proposed. PCOS patients commonly have hyperinsulinemia and insulin resistance which are also known risk factors for the development of diabetes mellitus, hypertension and cardiovascular disease. However, it is not known, how well the presence of PCOS symptoms would predict the appearance of the long-term sequelae of insulin resistance. Also more data is needed e.g. of the role of intrauterine factors and birth weight in the development of PCOS and hyperandrogenism.
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PMID:Polycystic ovary syndrome and hyperandrogenism as a risk factor for cardiovascular disease. 975 81

Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice.
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PMID:The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks. 1035 18


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