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)

Patients with congenital adrenal hyperplasia arising from mutations of 11beta-hydroxylase, the final enzyme in the glucocorticoid biosynthetic pathway, exhibit glucocorticoid deficiency, adrenal hyperplasia driven by unsuppressed hypothalamo-pituitary-adrenal activity, and excess mineralocorticoid activity caused by the accumulation of deoxycorticosterone. A mouse model, in which exons 3-7 of Cyp11b1 (the gene encoding 11beta-hydroxylase) were replaced with cDNA encoding enhanced cyan fluorescent protein, was generated to investigate the underlying disease mechanisms. Enhanced cyan fluorescent protein was expressed appropriately in the zona fasciculata of the adrenal gland, and targeted knock-out was confirmed by urinary steroid profiles and, immunocytochemically, by the absence of 11beta-hydroxylase. The null mice exhibited glucocorticoid deficiency, mineralocorticoid excess, adrenal hyperplasia, mild hypertension, and hypokalemia. They also displayed glucose intolerance. Because rodents do not synthesize adrenal androgens, changes in reproductive function such as genital virilization of females were not anticipated. However, adult homozygote females were infertile, their ovaries showing an absence of corpora lutea and a central proliferation of disorganized steroidogenic tissue. Null females responded normally to superovulation, suggesting that raised systemic progesterone levels also contribute to infertility problems. The model reveals previously unrecognized phenotypic subtleties of congenital adrenal hyperplasia.
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PMID:Cyp11b1 null mouse, a model of congenital adrenal hyperplasia. 1902 89

Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare, autosomal recessive form of congenital adrenal hyperplasia characterized by the coexistence of hypertension, caused by the hyperproduction of mineralocorticoid precursors and DSD in males and sexual infantilism in females, due to impaired production of sex hormones. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20-lyase deficiency have been reported previously. In the present study, we described a novel CYP17 mutation in two Brazilian sisters with primary amenorrhea, 46,XY karyotype, high basal levels of progesterone (3.4-4.9 ng/mL) and hypokalemic hypertension born to consanguineous parents. After PCR and automatic sequencing of CYP17 coding region, 25 bp duplication at exon 5 was found in the patients. This duplication started at codon 318 resulting in a premature stop codon at position 320 resulting in an ineffective and truncated protein and in accordance with the molecular modeling of P450c17. Therefore we expanded the repertoire of CYP17 mutations describing the largest duplication found in this gene in both sisters, with a clinical phenotype of combined 17alpha-hydroxylase/17,20-lyase deficiency and emphasizes the importance of the P450c 17 molecular modeling to predict the functional effect of these mutations.
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PMID:Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a homozygous 25 BP duplication (NT 4157-4181) at exon 5 in the CYP17 resulting in a premature stop codon predicted by molecular modeling. 1916 87

This series describes two patients with congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency. The first patient, a ten-year-old with XX genotype, reared as a male, presented with resistant hypokalaemia and hypertension. The second patient, a 23-year-old with XY genotype, presented with bilateral adrenal masses and resistant hypertension. Both the patients were offered bilateral adrenalectomy. These two patients are described with a discussion on the role of bilateral adrenalectomy in the management of difficult cases of congenital adrenal hyperplasia. The association of myelolipoma and testicular rests with this condition is also discussed.
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PMID:Congenital adrenal hyperplasia 11beta-hydroxylase deficiency: two cases managed with bilateral adrenalectomy. 1929 15

The knowledge of the genetic bases of hypertension has improved over the last decade; this area of research has high priority due to the high incidence of hypertension and its impact on public health. Monogenetic mineralocorticoid hypertension syndromes are associated with suppressed plasma renin activity due to excessive activation of the mineralocorticoid pathway. We review the pathophysiology, phenotype, and method of diagnosis for familial hyperaldosteronism type I and type II, hypertensive forms of congenital adrenal hyperplasia, 11beta-hydroxysteroid dehydrogenase type 2 deficiency, Liddle's syndrome, an activating mutation of the MR, and glucocorticoid resistance. We also review some genes that could contribute to essential hypertension.
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PMID:Genetics of hypertensive syndrome. 1933 89

The authors describe a case of an adult woman with congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency. The patient presented not only typical features of this disease such as virilization and hypokaliemic hypertension but also rare pathologies, such as ectopic adrenal tissues, salt loss during infancy, and functional adrenomedullary hyperactivity. In spite of the severe disease and delays in its diagnosis and adequate treatment, significant improvement in appearance and normalization of blood pressure as well as the birth of a healthy child were achieved. The paper also discusses current opinions concerning the pathogenesis and treatment in CAH with 11beta-hydroxylase deficiency as well as difficulties in diagnostic and therapeutic management.
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PMID:[Congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency. A case report]. 1934 18

In situations where the cause of hypokalemia is not obvious, measurement of urinary potassium excretion and blood pressure and assessment of acid-base balance are often helpful. A random urine potassium-creatinine ratio (K/C) less than 1.5 suggests poor intake, gastrointestinal losses, or a shift of potassium into cells. If hypokalemia is associated with paralysis, we should consider hyperthyroidism, familial or sporadic periodic paralysis. Metabolic acidosis with a urine K/C ratio less than 1.5 suggests lower gastrointestinal losses due to diarrhea or laxative abuse. Metabolic acidosis with K/C ratio of 1.5 higher is often due to diabetic ketoacidosis or type 1 or type 2 distal renal tubular acidosis. Metabolic alkalosis with a K/C ratio less than 1.5 and a normal blood pressure is often due to surreptitious vomiting. Metabolic alkalosis with a higher K/C ratio and a normal blood pressure suggests diuretic use, Bartter syndrome, or Gitelman syndrome. Metabolic alkalosis with a high urine K/C ratio and hypertension suggests primary hyperaldosteronism, Cushing syndrome, congenital adrenal hyperplasia, renal artery stenosis, apparent mineralocorticoid excess, or Liddle syndrome. Hypomagnesemia can lead to increased urinary potassium losses and hypokalemia. The differential rests upon measurement of blood magnesium, aldosterone and renin levels, diuretic screen in urine, response to spironolactone and amiloride, measurement of plasma cortisol level and the urinary cortisol-cortisone ratio, and genetic testing.
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PMID:Diagnosis of hypokalemia: a problem-solving approach to clinical cases. 1937 23

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired cortisol biosynthesis, with or without aldosterone deficiency, and androgen excess. Patients with the classic (severe) form also have epinephrine deficiency. Patients with CAH have an increased prevalence of risk factors for cardiovascular disease including obesity, hypertension, and insulin resistance. Androgen excess in women appears to be an additional risk factor for cardiovascular disease. Carotid intima-media thickness, a measure of subclinical atherosclerosis, also has been found to be increased in adults with CAH. The multiple hormonal imbalances present in the adult woman with CAH, in combination with chronic glucocorticoid therapy, contribute to cardiovascular disease risk. Further investigation of the predisposition to cardiovascular disease in women with CAH is warranted. Longitudinal studies are needed, and interventions targeting obesity, insulin resistance, hypertension, and hyperandrogenism may offer improved outcome.
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PMID:Cardiovascular disease risk in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 1953 65

17alpha-Hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia caused by mutations in the CYP17A1 gene. This condition shows considerable clinical and biochemical variation. Molecular characterization of novel mutations in the CYP17A1 gene and detailed study of their structural, enzymatic, and clinical consequences are required to fully understand enzyme behavior. Here, we present the first molecular characterization of two novel mutations in CYP17A1 in a 15-year-old female Mexican mestizo 46,XY female with primary amenorrhea and lack of pubertal development and severe hypertension that manifested only after surgery. A complete clinical and biochemical evaluation was compatible with 17OHD. Structural anomalies in the CYP17A1 gene were discovered by direct automated sequencing, which revealed a novel compound heterozygous K110X/R362H mutation that leads to a complete lack of enzyme activity. Immunohistochemical analyses performed to determine protein expression and localization showed that cytochrome P450 17A1 was completely absent in the patient's testicular tissue. Studies of novel mutations, such as those described here, provide important information that allows us to better understand the effect of a given mutation on enzyme function and to observe the impact of the mutation on clinical phenotype.
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PMID:Loss of cytochrome P450 17A1 protein expression in a 17alpha-hydroxylase/17,20-lyase-deficient 46,XY female caused by two novel mutations in the CYP17A1 gene. 1972 79

Adrenal diseases comprise for a variety of medical endocrine issues, ranging from partial or complete gland insufficiency, to several kinds of adrenal hyperfunction, either of congenital or neoplastic etiology. For hypofunction of the adrenals (partial or complete) the treatment of choice is medical; the mainstay of treatment is hydrocortisone. Patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency are treated with glucocorticoids to control androgen excess. Most benign neoplastic adrenal diseases that cause hyperfunction of the gland are surgically treated, however this may not be always feasible or effective. For Cushing's syndrome ketoconazole controls cortisol's hypersecretion, whereas in case of bilateral idiopathic hyperaldosteronism spironolactone controls hypokalemia and hypertension. For neoplastic adrenomedullary disease surgery is the treatment of choice; medical treatment is used preoperatively (mainly alpha blockers) and in case of disease persistence and /or recurrence (mainly metyrosine). For malignant adrenocortical disease, surgical removal remains the indicated treatment, but if the potential for surgical intervention is limited due to tumor extension, medical treatment can alleviate symptoms of hormone hypersecretion; mitotane in selected patients has good results.
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PMID:Medical management of adrenal disease: a narrative review. 1981 7

The treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is complex. In addition to disease control, important therapeutic goals are the maintenance of normal growth and the acquisition of normal reproductive function. Here, data regarding final adult height (FH) in patients with CAH will be reviewed. Additional difficulties associated with CAH, including risks of obesity and hypertension, will be discussed. Information about fertility and reproductive outcomes in men and women with CAH will also be summarized. Although the treatment of each child with CAH needs to be individualized, close medical followup and laboratory monitoring along with good compliance can often result in positive clinical outcomes.
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PMID:Growth and reproductive outcomes in congenital adrenal hyperplasia. 2014 87


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