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)

The human P450c17 alpha gene (CYP17) is a single copy gene located in chromosome 10, consisting of 8 exons and 7 introns. 17 alpha-Hydroxylase/17,20-lyase deficiency is one of two hypertensive forms of congenital adrenal hyperplasia and is inherited as an autosomal recessive trait; although rare, it probably exists with twice the frequency of the 11 beta-hydroxylase deficiency. Deficient 17 alpha-hydroxylation of pregnenolone and progesterone and subsequent deficiency of the cleavage of the C-17,20 carbon bond result in the absence of sex hormone formation in both the adrenal glands and the gonads, causing hypogonadism and male pseudohermaphroditism. Elevated and glucocorticoid-suppressible levels of the ZF 17-deoxysteroids--DOC and corticosterone--as well as their 18-hydroxylated products--18-OHDOC and 18-OHB (in addition to 19-nor-DOC)--are responsible for hypertension, hypokalemia, and renin and aldosterone suppression. A few cases, reported primarily among Japanese families, have basal hyperaldosteronism, an enigmatic condition that still demands adequate explanation. Like other forms of congenital adrenal hyperplasia, treatment of 17 alpha-hydroxylase deficiency consists of replacement doses of glucocorticoid hormones and supplemental estrogen therapy in the young adult patient. Heterozygotes may be detected by slightly exaggerated responses of some or all the ZF 17-deoxysteroids to ACTH stimulation, and by the elevated ratio of total urinary metabolites of corticosterone to the total metabolites of cortisol.
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PMID:Disorders of steroid 17 alpha-hydroxylase deficiency. 807 Apr 26

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Other findings include hypertension, diabetes mellitus and renal and cardiovascular anomalies. We have performed a genome-wide search for linkage in a large inbred Bedouin family. Pairwise analysis established linkage with the locus D16S408 with no recombination and a lod score of 4.2. A multilocus lod score of 5.3 was observed. By demonstrating homozygosity, in all affected individuals, for the same allele of marker D16S408, further support for linkage is found, and the utility of homozygosity mapping using inbred families is demonstrated. In a second family, linkage was excluded at this locus, suggesting non-allelic genetic heterogeneity in this disorder.
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PMID:Linkage of Bardet-Biedl syndrome to chromosome 16q and evidence for non-allelic genetic heterogeneity. 829 49

The combination of hypertension, hypokaliemia, and male pseudohermaphroditism or amenorrhea must prompt a search for a rare adrenal enzymatic defect, 17 alpha-hydroxylase/17,20-lyase deficiency. This is a report of the observation of a male patient in whom this rare deficit was diagnosed in adulthood on the basis of lifelong ambiguous external genitalia, hypogonadism, severe hypertension, bilateral adrenal hyperplasia, and biological markers evoking an excess of mineralocorticoids without hyperaldosteronism.
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PMID:Case report: 17 alpha-hydroxylase/17,20-lyase deficiency: a rare cause of endocrine hypertension. 878 79

17 alpha-Hydroxylase Deficiency (17 alpha-OHDS) is a rare defect of steroid biosynthesis, characterized by the inability to synthesize cortisol, androgens or estrogens, by the complete absence of follicular maturation, hypergonadotropic hypogonadism, primary amenorrhea and hypertension. Since the ovaries of such patients contain numerous primordial follicles, we hypothesized that the absence of spontaneous follicular maturation could be due to a lack of aromatizable substrate. To provide this substrate, testosterone was administered either by intra-ovarian injection or by vaginal administration. Ovarian stimulation was performed with human urinary gonadotropins. Follicular maturation and ovulation could be induced by this treatment, as determined from ultrasonography, the analysis of LH, estradiol and progesterone serum levels and the aspiration of oocytes from the mature follicles. Fertilization of these oocytes in vitro, however, did not succeed. We conclude that follicular maturation can be induced in 17 alpha-OHDS by gonadotropins when testosterone is provided as an aromatizable substrate and that estrogens are a necessary component of follicular maturation.
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PMID:Substitution with testosterone as aromatizable substrate for induction of follicular maturation, estradiol production and ovulation in a patient with 17 alpha-hydroxylase deficiency. 895 77

Primary empty sella syndrome (ESS) is an anatomo-radiological picture characterized by the presence of an arachnoid herniation filled with liquor that compresses the pituitary against the sellar wall. ESS occurs particularly in obese, hypertensive, cephalgic women, it is often asymptomatic but it may be associated with ophthalmologic, neurologic and sometime non-characterizing endocrine disorders. We report here 71 cases of primary ESS observed and assessed during the last fourteen years. The following endocrinological diagnostic procedures were carried out: hormonal (RIA) basal profile: FT3, FT4, TSH, PRL, ACTH, FSH, LH, 8.00 a.m. and p.m. cortisolemia, Aldo, PRA, DHEA-S, FTe, E2, P, PTH, CT, and calcemia and phosphoremia; provocative tests: TRH, GnRH, insulin hypoglycemia, etc.; inhibition tests: "overnight" and high dose dexamethasone. Clinical, radiological (skull radiographs, CT and/or MRI) and ophthalmologic (fundus, visual fields) assessment were made. We found principally cephalgia (52/71: 73.2%), hypertension (42/71: 59.1%), obesity (47/71: 66.1%). But we found especially mental disorders (57/71: 80.2%), in our knowledge not previously reported in the literature, as anxiety or dysthymic disorders with behavioural disturbances (chiefly oral compulsion). We found endocrinopathies in 36/71 (50.7%), isolated or coexisting in some patients: hyperPRL (14%), hypopituitarism (10.4%), hypogonadism (7%), diabetes insipidus (2.8%), hyperACTH (1.4%), hypoGH (15.4%), pituitary adenomas (8.4%). Several hypothalamic illness show a clinical picture including mental disorders and obesity. The Authors hypothesize that the ESS may be a "new" hypothalamic syndrome (compression/stretching on hypophysis and/or hypophyseal stalk by arachnoidocele; disorder of some hormones and neurotransmitters as leptin, neuropeptide Y, orexins, POMC-derived peptides, etc).
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PMID:[Primary empty sella syndrome. Observations on 71 cases]. 1020 96

Central or visceral obesity is recognized as a main risk factor for cardiovascular disease and type 2 diabetes mellitus. The co-existence of visceral obesity, increased blood lipid levels, hypertension and impaired glucose tolerance defines the metabolic syndrome that today is widely recognized as one of the prime factors behind cardiovascular morbidity and mortality. Endocrine disorders such as insulinoma, hypothyroidism and hypercortisolism are known to cause obesity. However, it is only hypercortisolism that is associated with increased abdominal fat accumulation. Recently, new findings have shed light on subtle endocrinopathies that are prevalent in individuals presenting with the metabolic syndrome. Such derangements are of borderline character and often fall within the normal reference range. Intervention studies demonstrate that correction of relative hypogonadism in men with visceral obesity and other manifestations of the metabolic syndrome seem to decrease the abdominal fat mass and reverse the glucose intolerance, as well as lipoprotein abnormalities in the serum. Further analysis of the underlying mechanism has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Longitudinal epidemiological data demonstrates that relatively low testosterone levels are a risk factor for development of visceral obesity. The primary event that triggers the initial development of visceral obesity is not known, but it seems plausible that increased activity in the hypothalamus-pituitary-adrenal axis can be of major importance.
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PMID:Androgens and abdominal obesity. 1033 65

We have previously demonstrated that genetically based leptin deficiency due to a missense leptin gene mutation in a highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. We have now performed detailed assessments of endocrine, sympathetic, and immune function. We have also identified a new adult female homozygous patient in this extended family who is severely obese and amenorrheic. In this family all wild-type and heterozgous individuals have normal body weight. Seven obese members of this family, whom we presume to have been leptin deficient, died during childhood. There are several findings that indicate potentially novel targets for leptin action in humans. Four homozygous patients (1 adult male, 2 adult females, and 1 child) have sympathetic system dysfunction, whereas all heterozygous subjects have normal sympathetic system function. Despite sympathetic system dysfunction and postural hypotension, 1 of 3 homozygous adult patients has impaired renin-aldosterone function. The patients also exhibit alterations in GH and PTH-calcium function, and 1 of them has decreased bone mineral density. Despite their obesity, these patients do not have risk factors for cardiovascular disease, such as hypertension, impairments in lipid metabolism, or hyperleptinemia [corrected]. These data support the hypothesis that the obese may have central, but not peripheral, resistance to the effects of leptin and that hyperleptinemia [corrected] may mediate the cardiovascular morbidity of the obese who are not leptin deficient. Furthermore, these data indicate that there may be several new targets for leptin action in human physiology. Such new targets may lead to novel pharmacological strategies for the use of leptin agonists and antagonists in the treatment of human disease. All 19 normal weight individuals in this family are alive, whereas 7 of 11 obese individuals died in childhood after infections. The odds ratio for mortality in the context of this obesity phenotype is 25.4, indicating that this mutation severely impairs key biological functions during childhood, negatively impacting on survival. We found that only the obese child in this family had thyroid function abnormalities. The oldest homozygous female patient started to menstruate, albeit with a luteal phase defect, 7 months ago, after a delay of over 20 yr, whereas the younger adult subjects are still hypogonadic. Thus, we conclude that due to their long life span, humans who survive the negative effects of leptin deficiency during childhood can, in contrast to ob/ob mice, over decades compensate some of the effects of leptin deficiency on immunity and endocrine function through mechanisms that remain to be elucidated.
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PMID:Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. 1183 53

The aim of this paper is to describe metabolic and endocrine alterations in the male, partners of infertile couples. One hundred and six consecutive men were taken in order to analyze their serum samples. Each serum sample was analyzed by duplicate for luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), free-testosterone (T), 17 alpha-hydroxyprogesterone (17OHP), androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S), prolactin (PRL), insulin, glucose, total cholesterol and triclylcerides. The data analysis evidenced different metabolic or endocrine alterations in the group. A dysplipidemia incidence of 65% was found (isolated hypercholesterolemia, isolated triglyceridemia or both), where 80% of these patients were younger than 40 years. There was no correlation with obesity, overweight any endocrine alteration and the type of sperm alterations. There was a positive correlation between E2 and FSH (r = 0.67, p < 0.0001) in the group of 106 patients, which remained significant in the group of hyperestrogenic men (n = 27, r = 0.68, p < 0.0001), but not in men with normal serum estrogen levels (n = 79, r = 0.10, NS). Other alterations: obesity in 18%, overweight in 30.2%, diabetes mellitus 4.7%, glucose intolerance 15%, hypertension 26% (14/53), hypergonadotropic hypogonadism 3.8% (one of them with an Emty Sella syndrome). Unexpectedly only nine patients (8.4%) out of the 106 consecutive patients recluted did not have any of the metabolic or endodrine abnormalities here described. These are more significant since 83% of the patients are younger than 40 years. The most interesting non previously described finding was the positive correlation observed between E2 and FSH when estradiol levels exceeds 50 pg/mL.
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PMID:[High incidence of hyperestrogenemia and dyslipidemia in a group of infertile men]. 1090 92

The objective of this study was to determine the efficacy and safety of sildenafil in patients with erectile dysfunction (ED) and associated organic risk factors in a multispecialty clinic. Patients (n = 521) were diagnosed with ED based on self-assessment. Associated risk factors were managed by medication or life-style modifications, or both, before treatment with sildenafil for ED. Patients received a 50-mg dose of sildenafil that could be adjusted to 100 mg or 25 mg based on tolerability and efficacy. Patients recorded the number of successful intercourse encounters for 6 to 8 weeks, and the number of adverse events. Overall, there was an 82% successful intercourse rate with sildenafil treatment. The predominant associated risk factors for ED were hypertension (39%), hypogonadism (37%), and multiple medications (34%). Common adverse events due to sildenafil treatment were mild to moderate in nature and resulted in <2% patient discontinuation. Clinicians should be particularly careful to evaluate patients presenting with ED because the condition can be accompanied by a wide spectrum of risk factors requiring monitoring and treatment. However, with adequate treatment and control of these risk factors, the use of sildenafil in a representative population of men with ED in a multispecialty clinic can achieve a higher efficacy rate than previous studies have indicated.
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PMID:Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors. 1154 91

Several issues should be addressed when managing women with Turner's syndrome. Female sex hormone substitution should be offered to help prevent the increased morbidity seen in Turner's women, which consists of an increased risk of fractures and osteoporosis, and a clustering of diseases such as ischaemic heart disease, hypertension, stroke and type 2 diabetes, the latter entities being part of the insulin resistance syndrome. Furthermore, hypothyroidism is often seen, and the risk of type 1 diabetes may also be increased. Congenital malformations of the heart are frequently seen in Turner's syndrome, possibly increasing the risk of dissecting aorta aneurysm. Liver enzymes are often elevated and there may be an increased risk of liver cirrhosis. Mortality seems to be increased in Turner's syndrome, women with the "pure" 45,X karyotype being the most severely affected. In clinical practice, careful monitoring of glucose and bone metabolism, weight, thyroid function and blood pressure should be carried out. A cardiovascular risk profile should be determined and the patient informed of the risks and benefits of sex hormone replacement therapy. Sex hormone replacement therapy is highly recommended, although at present there are no longitudinal data documenting the long-term positive effect of sex steroid substitution. However, hypogonadism is expected to explain at least part of the decreased lifespan found in Turner's syndrome. Since general physicians only encounter these patients infrequently, it is recommended that the care and treatment of Turner's syndrome be centralized.
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PMID:Medical problems of adult Turner's syndrome. 1178 85


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