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

While hypertension is observed in only two of the three major subtypes of congenital adrenal hyperplasia (CAH), 11 beta- and 17 alpha-hydroxylase deficiencies, deoxycorticosterone (DOC) production is increased in all. The elevated zona fasciculata (ZF) DOC produces mineralocorticoid hypertension with suppressed renin and reduced potassium concentrations. The DOC levels in 21-hydroxylase deficiency are in part produced by renin stimulation of the Zona glomerulosa (ZG) along with aldosterone. Assessment of the mineralocorticoid hormones of the ZF and ZF (17-deoxy steroids) provides additional unique characteristics of each subtype. Dissociation of DOC from cortisol is not unique to CAH. This dissociation is seen in other disorders and contrived conditions. There is a strong suggestion of a non-ACTH regulator of 17-deoxy steroids (DOC) that may contribute significantly to DOC production in general and effect DOC levels in CAH.
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PMID:Mineralocorticoids in congenital adrenal hyperplasia. 195 51

Studies in three families (A, B, and C) revealed five patients with congenital adrenal hyperplasia (CAH) due to partial and combined 21- and 11 beta-hydroxylase deficiency. One patient (A-11 1), a 23-yr-old severely virilized chromosomal female, was reared as a male, and two females (B-11 2 and C-1) complained only of hirsutism, acne, and menstrual abnormalities. Patients A-11 2 and B-11 8 (17 1/2 and 10 yr old) were asymptomatic and detected by finding an HLA genotype identical to that of their respectively affected brother and sister. Three patients (A-11 1, A-11 2, and C-1) had moderate hypertension. In spite of the wide range of clinical manifestations, all individuals had elevated androgen levels, while cortisol secretion was severely impaired only in A-11 2. 21-Hydroxylase deficiency was diagnosed on the basis of markedly increased plasma and urinary levels of 17-hydroxyprogesterone (17-OHP) and 21-deoxycortisol and their respective urinary metabolites pregnanetriol and pregnanetriolone. PRA was elevated in three patients, while urinary aldosterone was normal or increased. 11 beta-Hydroxylase deficiency was diagnosed on the basis of increased 11-deoxycortisol and deoxycorticosterone in plasma and tetrahydro-11-deoxycortisol and deoxycorticosterone in urine, particularly after ACTH administration. In contrast to classical 11 beta-hydroxylase deficiency CAH, urinary 18-hydroxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normal or elevated. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence in a single individual of the mutant genes for both 21- and 11 beta-hydroxylase deficiency CAH is very unlikely to occur. Two alternative hypotheses may explain our findings. One is the existence of a genetically inherited abnormal (or aberrant) 11 beta-hydroxylase, whose affinity for its normal substrate is changed for an abnormal one (17-OHP). As a result, 11 beta-hydroxylation of 11-deoxycortisol is deficient while 17-OHP 11 beta-hydroxylation is markedly enhanced. Thus, both 11-deoxycortisol and 21-deoxycortisol as well as their urinary metabolites accumulate. The ability for 18-hydroxylation, however, remains normal. In this case, 21-hydroxylase is not deficient, yet 21-deoxycortisol cannot be further hydroxylated to cortisol, since this steroid is not a suitable substrate for the enzyme. Such a disorder may represent a new allelic variant of 11 beta-hydroxylase deficiency CAH, which, similar to 21-hydroxylase deficiency, is completely linked to the HLA complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combined 21- and 11 beta-hydroxylase deficiency in familial congenital adrenal hyperplasia. 298 4

The 11 beta-hydroxylase deficiency (11OHD) form of congenital adrenal hyperplasia is diagnosed infrequently during the newborn period. A child presumed to have the 21-hydroxylase deficiency form of congenital adrenal hyperplasia was studied extensively as an infant. The diagnosis was based on ambiguous genitalia, elevated 17-ketosteroids, evidence of urinary 11-ketopregnanetriol, and salt loss. Severe hypertension was detected at 11 years, and 11 beta-hydroxylase deficiency was confirmed with elevated plasma 11-deoxycorticosterone and 11-deoxycortisol, low cortisol, and normalization of blood pressure following glucocorticoid replacement. Impaired aldosterone biosynthesis and salt loss were demonstrated during dexamethasone therapy. Salt loss during infancy does not distinguish between the 11 beta- and 21-hydroxylase deficiency forms of congenital adrenal hyperplasia.
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PMID:Neonatal salt loss in the hypertensive form of congenital adrenal hyperplasia. 696 49

Three patients, one male and two females, in whom the diagnosis of congenital adrenal hyperplasia (CAH) was made in early childhood were studied. The two females were treated with cortisone acetate from the age of 2 and 4 years, respectively, and later they both proved to be fertile. The male patient was only treated sporadically with cortisone acetate until the age of 33 years. He also became fertile when a more consistent treatment with prednisolone was started. The two female patients had a slight hypertension in childhood before the treatment was initiated but became normotensive on treatment. The male patient revealed a blood pressure of180/130 mm Hg at the age of 33 years. In this patient the treatment with prednisolone produced a moderate decrease in the blood pressure, but additional treatment with antihypertensive drugs was needed to make him normotensive. All three patients were originally thought to have a 21-hydroxylase deficiency and the correct diagnosis of an 11 beta-hydroxylase deficiency was first established between the age of 26 and 33 years. It is concluded that an early diagnosis and an uninterrupted treatment with glucocorticoids are important in order to prevent hypertension and infertility problems.
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PMID:Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency: final diagnosis in adult age in three patients. 735 68

Advances in technology have made possible the prenatal diagnosis and treatment of female fetuses with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hormonal measurement of 17-hydroxyprogesterone, androstenedione, testosterone and 21-deoxycortisol and HLA typing and DNA analysis for 21-OH/C4/HLA class I and II genes in chorionic villus cells and amniocytes are utilized for prenatal diagnosis. Maternal dexamethasone administration begun in the first trimester has prevented or ameliorated virilization in approximately three-fourths of infants. Maternal estriol levels appear to be the most accurate measure of fetal adrenal suppression. Maternal side effects are not infrequent and include excess weight gain, edema, glucose intolerance, hypertension and gastrointestinal problems. Severe permanent striae have been reported. Although no complications of prenatal treatment in the treated fetus or child have been reported long-term follow-up with careful neuropsychologic evaluation is not yet available and is necessary to fully evaluate possible long-term side-effects of prenatal dexamethasone treatment.
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PMID:Prenatal diagnosis and treatment of congenital adrenal hyperplasia. 782 Feb 12

Our research team and laboratories have concentrated on two inherited endocrine disorders, congenital adrenal hyperplasia (CAH) and apparent mineralocorticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficiency (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accumulate in excess and are converted to potent androgens, which are secreted and cause in utero virilization of the affected female fetus genitalia in the classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21-OHD, is the most common autosomal recessive disorder in humans, and occurs in 1/27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified that cause both classical and nonclassical CAH. Apparent mineralocorticoid excess is a potentially fatal genetic disorder causing severe juvenile hypertension, pre- and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of 11beta-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-renin hypertension.
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PMID:Steroid disorders in children: congenital adrenal hyperplasia and apparent mineralocorticoid excess. 1053 1

Prenatal diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is possible using chorionic villus and amniotic fluid cells for DNA analysis of the CYP21B gene and the C4 and HLA class I and II genes. Mutations can be identified on 95% of the chromosomes using Southern blot analysis and selective amplification of the CYP21B gene by polymerase chain reaction followed by allele-specific hybridization with oligonucleotide probes for a panel of nine known CYP21B mutations. Prenatal treatment with dexamethasone at doses between 0.5 and 2 mg/day is successful in three-quarters of the treated cases in eliminating or reducing the masculinization of the affected female external genitalia. The mother must be closely monitored for any adverse effects to her health such as hypertension or glucose intolerance. Prenatal dexamethasone treatment does not seem to have an adverse effect on growth, psychological development, or school performance except for increased shyness, internalizing and decreased social behavior. Animal studies, however, have shown abnormalities in the fetal brain and behavior of the animals. Prenatal dexamethasone treatment is still offered with caution to the parents of a potentially affected CAH female.
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PMID:Prenatal diagnosis and treatment of congenital adrenal hyperplasia and consequences in adults. 1196 26

A rare form of congenital adrenal hyperplasia (CAH), 11 beta-hydroxylase deficiency, may be misdiagnosed as 21-hydroxylase deficiency, the most common form of CAH, because of similar clinical presentations at times and elevated level of 17-hydroxyprogesterone in both conditions. We report a case of 11 beta-hydroxylase deficiency that was originally misdiagnosed as 21-hydroxylase deficiency. Hypertension and hypokalemia complicated with seizures and arrhythmia developed in this 9-year-old girl after abrupt withdrawal of oral dexamethasone but maintenance of fludrocortisone. Suspicion of 11 beta-hydroxylase deficiency led to DNA mutation analysis, which revealed a novel point mutation (CTG 461 CCG) in the CYP11B1 gene converting leucine to proline. Her condition stabilized rapidly after withdrawal of fludrocortisone and administration of hydrocortisone. Regular measurement of blood pressure should be performed in all patients with CAH and test of serum 11-deoxycortisol or deoxycorticosterone level should be performed in those patients with elevated blood pressure to avoid misdiagnosis of 11 beta-hydroxylase deficiency.
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PMID:Congenital adrenal hyperplasia with 11 beta-hydroxylase deficiency. 1554 55

The development of Cushing's disease among patients with deficiency of 21-hydroxylase has not been observed to date. The clinical manifestations and the hormonal profile of this exceptional association are herein described through the study of two cases. The first one was a 39-yr-old woman who had undergone non-curative transsphenoidal surgery for a pituitary-dependent Cushing's syndrome 12 yr before. She showed hypertension, central obesity, severe hirsutism, alopecia and hyperpigmentation. Urinary excretion of cortisol was normal, but ACTH levels were very high and hormonal dynamic studies (cortisol circadian rhythm, insulin-induced hypoglycemia and dexamethasone suppression tests) revealed the qualitative disturbances that characterize Cushing's disease. Serum concentrations of androstenedione, free testosterone and 17-hydroxyprogesterone were clearly increased. Reexamination of the tissue samples from previous surgery confirmed the presence of an ACTH-producing pituitary adenoma. CYP21 gene analysis found the splicing 655G mutation at intron 2 and the V281L mutation at exon 7. The second case was a 21-yr-old woman who was diagnosed with pituitary ACTH-dependent Cushing's syndrome according to unequivocal clinical and laboratory findings. However, hirsutism was particularly severe and both serum androgens and 17-hydroxyprogesterone were elevated. The patient was heterozygote for a large conversion of CYP21 gene. In these cases, the clinical and biochemical expression of Cushing's syndrome was determined by the different severity of 21-hydroxylase deficiency and the subsequent residual ability of adrenal cortex to synthesize cortisol.
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PMID:Clinical manifestations and hormonal profile of two women with Cushing's disease and mild deficiency of 21-hydroxylase. 1571 59

Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired adrenocortical and adrenomedullary function, and adrenal hyperandrogenism. Compared to normal subjects, patients with classic CAH have increased incidence of obesity and visceral adiposity, hyperinsulinism and insulin resistance, hyperleptinemia, hypertension, and hyperandrogenism. It is likely that the impaired adrenomedullary function and intermittent treatment-related hypercortisolism may account for the above abnormalities, and may predispose these subjects to the development of metabolic syndrome-related endothelial dysfunction and atherosclerotic cardiovascular disease in adulthood. Nonpharmacologic and pharmacologic interventions targeting obesity and/or insulin resistance may offer an improved outcome in terms of cardiovascular morbidity.
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PMID:Metabolic syndrome manifestations in classic congenital adrenal hyperplasia: do they predispose to atherosclerotic cardiovascular disease and secondary polycystic ovary syndrome? 1714 32


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