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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monogenic or single-gene forms of human hypertension result from mutations involving regulatory elements of the renin-angiotensin-aldosterone system (RAAS) or occur in syndromes associated with hereditary pheochromocytoma. RAAS gain-of-function mutations result in sodium retention, suppression of plasma renin activity, and often, but not invariably, hypokalemia. Hereditary RAAS syndromes result from intrinsic renal abnormalities (apparent mineralocorticoid excess and Liddle's syndromes) or from mineralocorticoid excess states (congenital adrenal hyperplasia and glucocorticoid-remediable aldosteronism). In the hereditary pheochromocytoma syndromes many asymptomatic individuals are identified because they are at-risk individuals in kindreds with a pheochromocytoma-predisposing syndrome. On the other hand, up to 25% of subjects with presumed "sporadic" pheochromocytoma have germline mutations in one of four pheochromocytoma susceptibility genes (the RET proto-oncogene, von Hippel-Lindau gene, neurofibromatosis F1 gene, and succinate dehydrogenase subunit D and succinate dehydrogenase subunit B genes). Hereditary pheochromocytomas are typically intra-adrenal and bilateral and patients typically present at younger ages compared with sporadic pheochromocytoma.
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PMID:Screening for genetic causes of hypertension. 1241 72

The most potent corticosteroids are 11beta-hydroxylated compounds. In humans, two cytochrome P450 isoenzymes with 11beta-hydroxylase activity, catalyzing the biosynthesis of cortisol and aldosterone, are present in the adrenal cortex. CYP11B1, the gene encoding 11beta-hydroxylase (P450c11), is expressed in high levels in the zona fasciculata and is regulated by adrenocorticotropic hormone (ACTH). CYP11B2, the gene encoding aldosterone synthase (P450c11Aldo), is expressed in the zona glomerulosa under primary control of the renin-angiotensin system. The substrate for P450c11 is 11-deoxycortisol. Mutations in CYP11B1 cause congenital adrenal hyperplasia (CAH) due to 11beta-hydroxylase deficiency. This disorder is characterized by androgen excess and hypertension and is autosomal recessively inherited. Classical and nonclassical forms of 11beta-hydroxylase deficiency can be distinguished. Studies in heterozygotes for classical 11beta-hydroxylase deficiency show inconsistent results with no or only mild hormonal abnormalities (elevated plasma levels of 11-deoxycortisol after ACTH stimulation). Molecular genetic studies of the CYP11B1 gene in 11beta-hydroxylase deficiency have led to the identification of several mutations. Transfection experiments showed loss of enzyme activity in vitro. Molecular genetic studies have practical importance for the prenatal diagnosis of virilizing CAH forms.
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PMID:Congenital adrenal hyperplasia: 11beta-hydroxylase deficiency. 1242 5

The case of a 15-yr-old boy with C11 hydroxylase deficiency congenital adrenal hyperplasia is reported who was diagnosed and treated as true precocious puberty at the age of 2 yr because of virilization and bilateral testicular enlargement. He later developed hyperpigmentation, hypertension and short stature and because of an increase in testes size he underwent testicular biopsy with the assumption of Leydig cell tumor. With the intake of glucocorticoids his testes size, hypertension and hyperpigmentation improved markedly. We could find only 6 such cases in the literature and have reviewed their clinical and laboratory data. All patients showed the picture of virilization with hypertension. Leydig cell tumor was proposed as the differential diagnosis in all cases except ours. Ultrasonography was able to show testicular adrenal-like tissue in all those in whom the procedure was undertaken. In the 5 patients of whom we could find enough data, 1 responded partially and 4 responded markedly to corticosteroid therapy with shrinkage of testicular tumors. We conclude that clinical findings and US are very important in the early diagnosis of these patients and with adequate treatment most cases show shrinkage in testicular tumors.
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PMID:Bilateral testicular enlargement due to adrenal remnant in a patient with C11 hydroxylase deficiency congenital adrenal hyperplasia. 1260 40

11beta-hydroxylase deficiency, an autosomal recessive disorder, is the second most common cause of congenital adrenal hyperplasia. We studied four subjects with classic 11beta-hydroxylase deficiency and severe hypertension: a 46,XX affected subject from a Turkish family with severe ambiguity of the external genitalia and hypertension, and three affected 46,XY subjects from a Dominican kindred with isosexual precocious puberty and severe hypertension. The affected subjects had significantly elevated plasma 11-desoxycortisol, 11-desoxycorticosterone, Delta4-androstenedione, and testosterone. To determine the molecular genetic defects, genomic DNA was isolated from the leukocytes of affected subjects and their family members. The encoding region of the 11beta-hydroxylase gene (CYP11B1) was amplified by PCR with specific primers. Using single-stranded DNA conformational polymorphism (SSCP) and DNA sequencing, a nonsense mutation in exon 6 of CYP11B1 in the affected 46,XX subject from the Turkish family was identified, where a cytosine was substituted by a thymidine, resulting in the replacement of glutamine (CAG) by a stop codon (TAG) at amino acid position 338 (Q338X). In the three 46,XY Dominican boys, the mutation was also a nonsense mutation in exon 6 of CYP11B1, where a cytosine was substituted by a thymidine, resulting in the replacement of glutamine (CAG) by a stop codon (TAG) at amino acid position 356 (Q356X). Both mutations result in the biosynthesis of a truncated 11beta-hydroxylase protein with loss of enzymatic activity. Heterozygosity was determined in family members of both probands including parents and siblings. These results indicate that mutations of CYP11B1 in these subjects are responsible for their clinical syndromes.
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PMID:Mutations in CYP11B1 gene: phenotype-genotype correlations. 1296 19

Adrenal disorders causing hypertension can be related to the dysfunction of either the adrenal cortex or the adrenal medulla. These disorders, including congenital adrenal hyperplasia (CAH), owing to 11B-hydroxylase deficiency and to 17alpha-hydroxylase deficiency; apparent mineralocorticoid excess; familial hyperaldosteronism type I; primary aldosteronism; Cushing's syndrome; and familial glucocorticoid resistance, primarily affect the adrenal cortex and cause low-renin hypertension. The classic disorder of the adrenal medulla resulting in hypertension is pheochromocytoma, although hypertension in obesity might also be associated with catecholamine secretion. In this review, we discuss these etiologies and the most recent advances in our knowledge of their pathophysiology, diagnosis, and treatment.
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PMID:Hypertension and adrenal disorders. 1459 71

Low-dose dexamethasone treatment is used in pregnancies where the fetus is suspected to be at risk of congenital adrenal hyperplasia (CAH). In order to see if such treatment had long-term effects, pregnant ewes were treated with dexamethasone (20 micro g/kg maternal body weight) or saline from 25 to 45 days of gestation and blood pressure and renal function studied in offspring at 2 Years of age. There were 11 animals from dexamethasone treatment (six females and five males) and nine lambs from saline treatment (five females and four males). We aimed to study blood pressure and heart rate in the adult animals of both genders, and renal function only in the adult female animals. In both females and males, blood pressure and heart rate were similar between the two groups of animals. The excretion rates of sodium and potassium were similar between the two groups of animals. In addition, glomerular filtration rate was not different between the two groups of animals (112+/-11 ml/kg per h (S.E.M.) in saline-treated females vs 112+/-10 ml/kg per h in dexamethasone-treated females). There were no differences in body weight or weights of the kidney and heart between the treatments in both females and males. In conclusion, these results are reassuring for patients similarly exposed to prenatal dexamethasone treatment for CAH, as in our animal model no evidence of altered renal function or predisposition to adult hypertension was found.
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PMID:Prolonged low-dose dexamethasone treatment, in early gestation, does not alter blood pressure or renal function in adult sheep. 1459 79

Congenital adrenal hyperplasia (CAH) refers to a family of inherited disorders of adrenal steroidogenesis in which each disorder is characterized by a specific enzyme deficiency that impairs cortisol production by the adrenal cortex. The enzymes most commonly affected are 21-hydroxylase (21-OH), 11beta-hydroxylase, 3beta-hydroxysteroid dehydrogenase, and less often, 17alpha-hydroxylase/17,20-lyase and cholesterol desmolase. Many of the corresponding genes for the described enzymes have been isolated and characterized, and specific mutations causing CAH have been identified. In classical CAH (simple virilizing and salt wasting forms), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in both sexes. In nonclassical CAH, 21-OHD is partial and occurs with milder symptoms. A deficiency of 11beta-Hydroxylase deficiency results in ambiguous genitalia in the newborn genetic female and androgen excess and hypertension in both males and females. In 3beta-hydroxysteroid deficiency adrenal and gonadal androgen production is deficient resulting in incomplete genital development in genetic males and limited androgen affect in females. Two less frequent causes of CAH 17alpha-Hydroxylase/17,20-lyase and cholesterol desmolase result in external female genitalia in both sexes. Hormonal diagnosis is described for each disorder.
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PMID:Inborn errors of adrenal steroidogenesis. 1465 79

P450c17 deficiency is an autosomal recessive disorder and a rare cause of congenital adrenal hyperplasia characterized by hypertension, hypokalemia, and impaired production of sex hormones. We performed a clinical, hormonal, and molecular study of 11 patients from 6 Brazilian families with the combined 17alpha-hydroxylase/17,20-lyase deficiency phenotype. All patients had elevated basal serum levels of progesterone (1.8-38 ng/ml; 0.57-12 pmol/liter) and suppressed plasma renin activity. CYP17 genotyping identified 5 missense mutations. The compound heterozygous mutation R362C/W406R was found in 1 family, whereas the homozygous mutations R96W, Y329D, and P428L were seen in the other 5 families. The R96W mutation has been described as the cause of p450c17 deficiency in Caucasian patients. The other mutations were not found in 50 normal subjects screened by allele-specific oligonucleotide hybridization (Y329D, R362C, and W406R) or digestion with HphI (P428L) and were recently found in other Brazilian patients. Therefore, we elucidated the genotype of 11 individuals with p450c17 deficiency and concluded that basal progesterone measurement is a useful marker of p450c17 deficiency and that its use should reduce the misdiagnosis of this deficiency in patients presenting with male pseudohermaphroditism, primary or secondary amenorrhea, and mineralocorticoid excess syndrome.
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PMID:P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping. 1467 Nov 62

The results of many studies performed on animals and humans strongly suggest that genetic factors lead to the development of hypertension (HT). Syndromes in which mutations in single genes are sufficient to result in large changes of blood pressure are rare. Nevertheless, it is anticipated that their understanding will lead to new insights into forms of hypertension occurring more often, including essential hypertension. At least 9 monogenic forms of HT including Liddle syndrome, type I familial hyperaldosteronism (GRA) and type II familial hyperladosteronism, Gordon syndrome, apparent mineralocorticoid excess syndrome (AME), hypertension associated with type E brachydactyly, glucocorticoid receptor mutations, type IV congenital adrenal hyperplasia (CAH) (11 beta-hydroxylase deficiency), and type V CAH (17 alpha-hydroxylase deficiency) have been described so far.
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PMID:[Monogenic hypertension]. 1505 25

Primary aldosteronism, congenital adrenal hyperplasia, Cushing's syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also, new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing's syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.
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PMID:Adrenocortical hypertension. 1648 Jun 76


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