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)

Late-onset congenital adrenal hyperplasia is a cause of a spectrum of clinical manifestations of postnatal androgen excess. In these cases, ACTH stimulation test with measurement of 17-Hydroxyprogesterone (17OHP) is usually done to assess 21-hydroxylase (21-OH) deficiency. Determination of the 11-deoxycortisol (S) and the S to cortisol ratio is rarely done, so that 11 beta-hydroxylase (11-OH) deficiency seems unusual. We systematically investigated this biosynthetic defect among women complaining of hyperandrogenism (n = 519) and, comparing the patient's hormonal responses to ACTH with those of 31 normal women, found 29 11-OH deficiency (5.6%): this is the largest group ever reported. S was elevated only 9 times, so that using this single determination, diagnosis of 20 enzymatic defects would not have been made. Only three of the patients (10%) had hypertension, even though the pathway of aldosterone was involved in 33% of cases (criteria: elevation of the ratio desoxycorticosterone to corticosterone). We also described one new patient with both 11-OH and 3-beta-hydroxysteroid dehydrogenase deficiencies. The patho-physiology is particularly interesting in these cases. It is concluded that the single research for 21-OH deficiency is inadequate among women complaining of hyperandrogenism: the screening for 11-OH deficiency should be made, even if blood pressure is normal.
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PMID:[Adrenal enzymatic block with late-onset caused by 11-hydroxylase deficiency. Apropos of 29 cases]. 134 Jun 85

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

A 60-year-old woman presented with a history of palpitations, headaches and severe hypertension, which was resistant to hypotensive agents. She had a 2-year history of obesity and a moon face. Her plasma adrenocorticotropic hormone level was below the limits of detection and did not respond to corticotropin-releasing hormone. Urinary-free cortisol was elevated and the circadian rhythm of serum cortisol level had completely disappeared. Imaging analysis demonstrated a unilaterally functioning mass in the left adrenal gland. Serum cortisol level in the left adrenal vein was elevated. The resected adrenal mass measured 4 x 3.5 x 2.5 cm, and ranged from yellow to tan in color. The adrenal cortex adjacent to the nodule did not demonstrate cortical atrophy. The mass was well circumscribed but not encapsulated, and consisted of multiple cortical nodules. These nodules were composed predominantly of clear cortical cells, and partly of compact cortical cells. Immunoreactivity of steroidogenic enzymes including cholesterol side-chain-cleavage P450, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase cytochrome P450, 11beta-hydroxylase cytochrome P450 and 17alpha-hydroxylase cytochrome P450 was marked in cortical nodules, but minimal in non-nodular cortex. Ultrastructural examination of nodular cortical cells also demonstrated well-developed mitochondria and smooth endoplasmic reticulum, consistent with elevated steroidogenesis in these cells.
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PMID:Adrenocorticotropin-independent unilateral adrenocortical hyperplasia with Cushing's syndrome: Immunohistochemical studies of steroidogenic enzymes, ultrastructural examination and a review of the literature. 1116 51

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.
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PMID:Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling. 1188 72

Data related to genetics of congenital adrenal hyperplasia with emphasis on CYP21 gene defects are briefly outlined. Mutations of the StAR gene lead to impaired translocation of cholesterol from the outer mitochondrial membrane to the inner mitochondria, a rate limiting step in steroidogenesis in the adrenals and the gonads. The clinical picture is characterized by adrenal and gonadal insufficiency and sex reversal in XY individuals. Molecular defects of the CYP17 gene encoding 17alpha-hydroxylase can cause hypertension, impaired sexual maturation and impaired sexual differentiation in XY individuals. Molecular defects of the CYP11B1 gene lead to 11-hydroxylase deficiency, which is clinically expressed with virilization of the external genitalia of the female and precocious puberty in the male, as well as hypertension in both sexes. The HSD3beta1 and HSD3beta2 genes encode two isoenzymes (3betaHSDI and 3betaHSDII). The clinical picture results from either absence or diminished activity of type II 3betaHSD, resulting from mutations of the HSD3beta2 gene. The most frequent form of CAH (90% of all patients) is due to deletions, conversions or point mutations of the CYP21 gene, which encodes the enzyme 21-hydroxylase. There is a wide range of clinical expression primarily explained by the type of the molecular defect. The ratio of genotype to phenotype concordance varies in the different forms of the disease, the highest one being encountered in the non-classical form. Heterozygosity of CYP21 mutations may be expressed as premature pubarche.
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PMID:Genetic aspects of congenital adrenal hyperplasia. 1196 27

Hypertrichosis, characterized by increased hair growth located in non-androgen-dependent areas, does not justify the monitoring of hormone levels, conversely to hirsutism, with increased hair growth in androgen-dependent areas of the female genitals. Adult hypertrichosis is iatrogenic (minoxidil, ciclosporine, diazoxide or glucocorticosteroids), of metabolic origin (porphyria), nutritional (anorexia) or paraneoplastic (hypertrichosis lanuoginosa). Metabolic or general assessment can help clinical diagnosis. In non-iatrogenic hirsutism the following must be eliminated: 1) a virilizing tumor (ovarian, adrenal) when confronted with rapid progression or recent hirsutism, plasma testosterone (T)>1.5ng/ml and/or (adrenal tumor) DHEA-sulfate (DHEAS)>700 microgram/dl and associated with hypertension; 2) when confronted with characteristic signs of hirsutism, Cushing's syndrome (post-dexamethasone cortisol), hyperprolactinemia (pooled PRL), or acromegalia (IGF1). Measurement of 17-OH-progesterone at 8 am on the 4th day of the cycle detects the late manifestation homozygous forms of a 21-hydroxylase (21OHD) block. The more frequent forms are: 1) ovarian polymicrocystic or hirsutism-anovulation syndromes without other causes (LH/FSH, T, hyperinsulinemia, sonography); 2) functional adrenal hyperandrogenia (increased DHEAS without organic cause); 3) idiopathic hirsutism. Treatment can be local (discoloration, depilation, diathermo-coagulation, laser). Treatment of hirsutism of organic origin is etiologic. The inhibitory effects of glucocorticosteroids are mediated by 21OHD. The most effective treatments are anti-androgenic: cyproterone acetate, progesterone-like and anti-gonadotropic (contraceptive) agents; and the only product in France officially indicated in hirsutism , spironolactone (anti-mineralocorticosteroid); and flutamide, pure anti-androgen (probably hepatoxic). Finasteride (type II 5 alpha-reductase inhibitor) appears less effective. Estrogen-progestagen-like agents can be associated with anti-androgens. We should also mention the GnRH-agonists, and finally, dietetics and metformine (in cases of insulin-resistance).
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PMID:[Hirsutism and hypertrichosis in adults: investigations and treatment]. 1222 63

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

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

This paper is a review of the literature about adrenal myelolipoma. It is a rare, benign, hormonally inactive tumor of the adrenal gland composed of mature fat tissue and hematopoietic tissue in varying amounts. Adrenal myelolipoma is usually small (< 4 cm), unilateral and causes no clinical disorders. The age range of the affected patients is 20-90 years; most are men in their fourth to sixth decade. This tumour is discovered during autopsy or USG, CT MRI of the abdomen usually by chance and because of that is included in the group of tumors called incidentaloma. Etiology of myelolipoma is unclear. It is usually hormonally inactive but there were several cases in which adrenal myelolipoma coexisted with various endocrine disorders such as Cushing's syndrome, Conn's syndrome, Addison's disease, hirsutism, hermaphroditism, inborn deficiencies of 17- and 21-hydroxylase. It is also more frequent in patients with obesity, hypertension and leading stressful life. Surgical treatment is called for when the diameter of tumor reaches more than 4 cm, tumour shows tendency to fast growth or causes clinical disorders. In cases of small lesions, that show no progression, it is advised to observe the tumor using imaging techniques.
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PMID:[Adrenal myelolipoma]. 1585 62

We present a 39-year old female with a benign adrenal tumor characterized by autonomous secretion of cortisol, androgens, and aldosterone. The patient presented with a 4-year history of hypertension and severe hirsutism. Baseline investigations revealed elevated testosterone, androstendione, and 17OH progesterone with normal levels of dehydroepi androsterone sulfate. CT of the adrenals revealed a 2.5 x 3.0 cm tumor with characteristics of an adenoma on the left adrenal gland. Pelvic ultrasound was normal. Further investigations revealed suppressed basal ACTH levels, loss of diurnal rhythm of cortisol, and failure to suppress on low dose dexamethasone suppression test, suggesting autonomous cortisol secretion by the tumor. She had an exaggerated response of 17OH progesterone to ACTH, implying reduced 21-hydroxylase activity. An elevated plasma aldosterone concentration to plasma renin activity ratio was suggestive of hyperaldosteronism, which was confirmed by failure of aldosterone to suppress to a formal saline infusion test. Complete clinical and biochemical remission of the disease was observed after left adrenalectomy. Histology confirmed the presence of an adrenocortical adenoma. The patient developed multiple sclerosis 6 months after the operation. The flare-up of an autoimmune disease (multiple sclerosis) postoperatively could be coincidental or possibly related to the high normalization of the high cortisol levels acting as a precipitating factor.
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PMID:A unique case of a benign adrenocortical tumor with triple secretion of cortisol, androgens, and aldosterone: development of multiple sclerosis after surgical removal of the tumor. 1661 21


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