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)

In a 19-year-old phenotypic female (46, XY) with hypertension and hypokalemia, studies confirmed 17-alpha-hydroxylase deficiency. Prior to diagnosis she had been considered to have testicular feminization. Increased plasma progesterone and urinary pregnanediol levels were present before treatment. Increased secretion rates of deoxycorticosterone and corticosterone and abnormally low production of cortisol and aldosterone were present. Following treatment with hydrocortisone, plasma progesterone, serum potassium, and urinary pregnanediol levels and DOC and B secretions were normal. Aldosterone secretion six months after treatment remained low. Normal blood pressure measurements were achieved during treatment with hydrocortisone and oral estrogen with the patient at rest; however, mild elevations in blood pressure (130/90 mm Hg) have been noted despite continued hydrocortisone therapy.
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PMID:Studies in a phenotypic female with 17-alpha-hydroxylase deficiency. 18 44

This is a case report of a 43 years old phaenotypic female (karyotype 46 XY) with congenital adrenal hyperplasia and male pseudohermaphroditism presenting with severe hypertension and hypokalaemic alkalosis. Evaluation of the steroid biosynthesis of the adrenals as well as of the intraabdominal testes demonstrated a severe degree of 17-alpha-hydroxylase deficiency in this patient. This defect was associated by a complete lack of deoxycortisol and cortisol as well as of testicular testosterone synthesis, and by an overproduction of DOC and corticosterone. Sruvival of the patient in spite of severe cortisol deficiency was due to the glucocorticoid activity of corticosterone. This compound and DOC account also -- due to their mineralocorticoid properties -- for the hypertensive state of this male pseudohermaphrodite.
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PMID:Hypergonadotrophic male pseudohermaphroditism due to complete 17-alpha-hyroxylase deficiency. 91 71

The discovery of testicles in a 3-year-old girl with XY karyotype led to a diagnosis of testicular feminization. Subsequently, however, hypokalaemia, hypertension, and severe prostration during a mild infection suggested adrenal involvement, and investigations showed a 17-alpha-hydroxylase deficiency. Diagnosis of testicular feminization should not be made without excluding a defect of testosterone synthesis.
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PMID:Female phenotype in a male child due to 17-alpha-hydroxylase deficiency. 99 30

We have studied a family (12 members) with 3 patients (2 adult females and 1 pubertal-aged genotypic male) affected by congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency, all of whom presented as phenotypically female subjects with lack of sexual development and with hypokalemic hypertension. The baseline hormonal pattern revealed low glucocorticoid levels (17-hydroxyprogesterone, plasma and urinary cortisol, cortisol secretion rate), as well as androgen (testosterone and dehydroepiandrosterone sulfate) and estrogen (17-beta-estradiol) levels, since the defect is present at both adrenal and gonadal levels. As a consequence ACTH, LH, and FSH concentrations were high. Otherwise steroids not requiring 17-alpha-hydroxylation, such as deoxycorticosterone, corticosterone and their 18-hydroxylated compounds, were secreted in excess with the exception of aldosterone whose levels were undetectable; baseline plasma renin activity levels were suppressed. Short-term dexamethasone treatment normalized potassium and reduced blood pressure and the abnormal mineralocorticoid levels. During chronic ACTH suppression with low doses of glucocorticoids (8 years), electrolyte disturbances were corrected, blood pressure was normalized in 2 cases but only reduced in the third; plasma renin activity returned to normal range within four years in all the patients, while urinary aldosterone was normalized only after 8 years of therapy and became partially responsive to posture, ACTH, angiotensin II, and furosemide. The other mineralocorticoids were reduced but remained above the normal range. The HLA-genotyping in all the family members revealed that the gene responsible for 17-alpha-hydroxylase deficiency was not linked to the HLA system. Measurement of plasma steroids (deoxycorticosterone, corticosterone, aldosterone) in this family revealed that the heterozygotes were different from the control population only in their ACTH-stimulated corticosterone levels.
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PMID:17-alpha-hydroxylase deficiency in three siblings: short- and long-term studies. 164 17

17 alpha-Hydroxylase deficiency is characterized by defects in either or both of the 17 alpha-hydroxylase/17,20-lyase activities. We have elucidated the molecular basis of the combined deficiency of these activities in a Japanese female who is genotypically male and the child of a consanguineous marriage. The complete exonic sequence of the patient's CYP17 (P45017 alpha) gene revealed a seven-basepair duplication (GCGCACA) in exon 2 which leads to a frame shift and, subsequently, a premature stop codon. Because this stop codon occurs N-terminal to the heme-binding sequence, the presence of this mutation leads to the absence of a functional P45017 alpha-protein in adrenal cortex and testis. This, in turn, leads to an absence of sex steroids and excessive secretion of steroids with mineralocorticoid activity and, consequently, female external genitalia and hypertension in this 46XY patient.
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PMID:Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a 7-basepair duplication in the N-terminal region of the cytochrome P45017 alpha (CYP17) gene. 233 73

Adrenal hyperplasia due to 17-alpha-hydroxylase deficiency is coupled with precocious hypogonadism, which causes pseudohermaphroditism in XY subjects and primary amenorrhea in XX subjects. The physiology of gluco- and mineral-corticoid adrenal activity, as well as the biosynthesis of gonadal steroids, is totally altered. We report two cases of XY subjects, identified as females, who came to our observation for primary amenorrhea and exhibited a hypertension with hypokaliemia. We also report a critical review of the literature, with a main attention to differential diagnosis and mineralcorticoid physiopathology, in order to contribute to the knowledge of normal adrenal function and of this enzymatic defect.
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PMID:[Male pseudohermaphroditism caused by 17-alpha-hydroxylase deficiency. Personal case reports and a review of the literature]. 269 23

17 alpha-Hydroxylase deficiency blocks the biosynthesis of cortisol and sex steroids, resulting in mineralocorticoid excess, hypertension, sexual infantilism, and female phenotype in both genetic sexes. The disease is caused by mutations in the gene encoding cytochrome P450c17, which is the single enzyme that mediates both 17 alpha-hydroxylase and 17,20-lyase activities. We report a 14-yr-old patient from Thailand with a classical clinical presentation of this rare disorder. Analysis of her P450c17 gene by polymerase chain reaction amplification and sequencing showed a nine-base deletion, eliminating codons 487-489 (Asp-Ser-Phe) near the carboxy-terminus of P450c17. This deletion creates a BclI site in the mutant DNA, permitting accurate demonstration that the patient was homozygous for this lesion, whereas one parent and two siblings were heterozygous. By use of site-directed mutagenesis, we created a vector that could express this mutated form of P450c17 when transfected into non-steroidogenic COS-1 cells. Such transfected cells produced immunodetectable P450c17 protein, but had no 17 alpha-hydroxylase or 17,20-lyase activity, whereas cells similarly transfected with a vector expressing normal human P450c17 could 17 alpha-hydroxylate either pregnenolone or progesterone and convert 17 alpha-hydroxypregnenolone to dehydroepiandrosterone, showing the presence of both activities. This is the first report of the molecular genetic basis of 17 alpha-hydroxylase deficiency in a Southeast Asian patient.
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PMID:Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency. 834 56

A case of 17-alpha-hydroxylase deficiency in a genotypic male is described. The patient, who had grown up as a female, at the age of 18 years by chance was seen for enteritis. She presented primary amenorrhea and lack of secondary sexual characteristics combined with hypertension and mild hypokalemia due to excess of mineralcorticoids. The hormonal profile observed under basal conditions was evocative of a deficiency in 17-alpha-hydroxylase. High plasma aldosterone concentrations, in the face of suppressed PRA, were related to interference in RIA method: low plasma aldosterone values were observed when HPLC separation was applied. Eunucoid appearance and gigantism (195 cm) has rarely been observed as a fenotypic expression of this enzymatic deficit, but are justified by deficiency of both androgens and estrogens.
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PMID:[Male pseudohermaphroditism due to 17-alpha-hydroxylase deficiency]. 870 21

A 36 year old white female came to our service after having been evaluated on repetitive occasions in the past for a workup of gigantism and acromegalic features. Since childhood she had developed tall stature, frontal bossing, prominence of zygomatic bones, separated teeth, large hands and size 14 shoes. Human growth hormone and somatomedin serum levels had been normal on all occasions tested. Her past history was significant for primary amenorrhea and a 12 year history of hypertension. On physical examination BP was 140/100, height 6' 2", weight 2571 bs. Her phenotype was truly acromegalic. There was absence of axillary and pubic hair with no breast development. External genitalia was of female appearance. Laboratory evaluation showed increased FSH of 88 mlU/ml, increase LH of 65.6 mlU/ml and decreased E2 of 12.6 pg/ml. Other findings were low serum cortisol of 0.2 mg/dl, high ACTH of 344 pg/ml, low 17-Ketosteroids, high pregnenolone levels of 595 mg/dl, low 17-hydroxypregnenolone less than 10 ng/dl, very high aldosterone of 31 ng/dl and suppressed PRA of less than 0.1 ng/ml. A pelvic sonogram showed a right ovoid structure which could represent a gonad and failed to identify the uterus and left gonad. A bone densitometry showed a decrease bone mineral density compatible with osteoporosis. Chromosome study showed a karyotype of 46-XY. A diagnosis was made of congenital adrenal hyperplasia secondary to 17-alpha-hydroxylase deficiency in a genotypic male. Our patient was referred to the department of gynecology for surgical removal of the gonads. It is amazing how a patient with severe adrenal insufficiency can withstand 36 years of her life undiagnosed without going into an adrenal crisis. Her tall stature and acromegalic features were the striking signs confusing all physicians and delaying the correct diagnosis and appropriate treatment. There has been reported worldwide, nearly 120 cases with documented severe 17-alpha-hydroxylase deficiency. To our knowledge this is the first case identified in Puerto Rico of male pseudohermaphroditism secondary to 17-alpha-hydroxylase enzyme deficiency.
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PMID:[Male pseudohermaphroditism caused by enzymatic deficiency of 17-alpha-hydroxylase. 1st case reported in Puerto Rico]. 957 56

Congenital adrenal hyperplasia is an uncommon diagnosis in routine clinical practice. 21-hydroxylase deficiency, which is its most common subtype, may be diagnosed at birth in a female infant by virilisation or by features of salt wasting in both genders. However, other uncommon subtypes of this condition such as 17-alpha-hydroxylase deficiency, 11-beta-hydroxylase deficiency may present much later in adolescence or adulthood. A high index of suspicion is necessary when evaluating children with hypertension, hypokalaemia, metabolic alkalosis or sexual infantilism.
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PMID:Congenital adrenal hyperplasia masquerading as periodic paralysis in an adolescent girl. 2281 32


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