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| {{CMG}} | | {{11β-hydroxylase deficiency}} |
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| | '''For patient information, click [[{{PAGENAME}} (patient information)|here]].''' |
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| | {{CMG}}; {{AE}} {{MJ}} |
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| '''11β-Hydroxylase deficient congenital adrenal hyperplasia''' ('''11β-OH CAH''') is an uncommon form of [[congenital adrenal hyperplasia]] resulting from a defect in the [[gene]] for the [[enzyme]] which mediates the final step of [[cortisol]] synthesis in the [[adrenal gland|adrenal]]. 11β-OH CAH results in [[hypertension]] due to excessive [[mineralocorticoid]] effects. It also causes excessive [[androgen]] production both before and after birth and can [[virilization|virilize]] a genetically female fetus or a child of either sex.
| | {{SK}} 11 beta hydroxylase deficiency; 11b hydroxylase deficiency; 11 b hydroxylase deficiency; 11b-hydroxylase deficiency; 11-b-hydroxylase deficiency; Adrenal hyperplasia, hypertensive form; Deficiency of steroid 11-beta-monooxygenase; P450C11B1 deficiency; Steroid 11 beta hydroxylase deficiency; 11 hydroxylase deficiency. |
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| ==What is CAH?==
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| ''Congenital adrenal hyperplasia'' (CAH) refers to any of several [[autosomal]] [[recessive]] diseases resulting from defects in steps of the [[synthesis]] of [[cortisol]] from [[cholesterol]] by the [[adrenal gland]]s. All of the forms of CAH involve excessive or defective production of [[sex steroid]]s and can pervert or impair development of [[primary sex characteristic|primary]] or [[secondary sex characteristic]]s in affected infants, children, and adults. Many also involve excessive or defective production of [[mineralocorticoid]]s, which can cause [[hypertension]] or salt wasting.
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| The most common type of CAH is due to [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency|deficiency of 21-hydroxylase]]. 11β-Hydroxylase deficient congenital adrenal hyperplasia is one of the less common types of CAH due to deficiencies of other proteins and enzymes involved in cortisol synthesis. Other uncommon types are described in individual articles (links below).
| | ==[[11β-hydroxylase deficiency overview|Overview]]== |
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| ==11β-Hydroxylase deficient CAH== | | ==[[11β-hydroxylase deficiency historical perspective|Historical Perspective]]== |
| 11β-OH CAH resembles [[congenital adrenal hyperplasia|21-hydroxylase deficient CAH]] in its [[androgen]]ic manifestations: partial [[virilization]] and [[ambiguous genitalia]] of genetically female infants, childhood virilization of both sexes, and rarer cases of virilization or [[infertility]] of adolescent and adult women. The [[mineralocorticoid]] effect differs: [[hypertension]] is usually the clinical clue that a patient has 11- rather than 21-hydroxylase CAH. Diagnosis of 11β-OH CAH is usually confirmed by demonstration of marked elevations of 11-deoxycortisol and 11-deoxycorticosterone (DOC), the substrates of 11β-hydroxylase. Management is similar to that of 21-hydroxylase deficient CAH except that mineralocorticoids need not be replaced.
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| ===Pathophysiology of 11β-OH CAH===
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| The enzyme which mediates 11β-hydroxylase activity is now known as P450c11β since it is one of the [[cytochrome P450 oxidase]] enzymes located in the inner [[mitochondrion|mitochondrial]] membrane of cells of the adrenal cortex. It is coded by a gene at 8q21-22. Like the other forms of CAH, a number of different defective alleles for the gene have been identified, producing varying degrees of impaired 11β-hydroxylase activity. Also like the other forms of CAH, 11β-OH CAH is inherited as an autosomal recessive disease.
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| 11β-Hydroxylase mediates the final step of the [[glucocorticoid]] pathway, producing cortisol from 11-deoxycortisol. It also catalyzes the conversion of 11-deoxycorticosterone (DOC) to [[corticosterone]] in the [[mineralocorticoid]] pathway.
| | ==[[11β-hydroxylase deficiency classification|Classification]]== |
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| ===Mineralocorticoid aspects of 11β-OH CAH=== | | ==[[11β-hydroxylase deficiency pathophysiology|Pathophysiology]]== |
| [[Mineralocorticoid]] manifestations of severe 11β-hydroxylase deficient CAH can be biphasic, changing from deficiency (salt-wasting) in early infancy to excess ([[hypertension]]) in childhood and adult life. | |
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| Salt-wasting in early infancy does not occur in most cases of 11β-OH CAH but can occur because of impaired production of [[aldosterone]] aggravated by inefficiency of salt conservation in early infancy. When it occurs it resembles the salt-wasting of severe [[congenital adrenal hyperplasia|21-hydroxylase deficient CAH]]: poor weight gain and vomiting in the first weeks of life progress and culminate in life-threatening [[dehydration]], [[hyponatremia]], [[hyperkalemia]], and [[metabolic acidosis]] in the first month.
| | ==[[11β-hydroxylase deficiency causes|Causes]]== |
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| Despite the inefficient production of aldosterone, the more characteristic mineralocorticoid effect of 11β-OH CAH is hypertension. Progressive adrenal hyperplasia due to persistent elevation of ACTH results in extreme overproduction of 11-deoxycorticosterone (DOC) by mid-childhood. DOC is a weak mineralocorticoid, but usually reaches high enough levels in this disease to cause effects of mineralocorticoid excess: salt retention, volume expansion, and [[hypertension]].
| | ==[[11β-hydroxylase deficiency differential diagnosis|Differentiating 11β-hydroxylase deficiency From Other Diseases]]== |
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| ===Sex steroid effects of 11β-OH CAH=== | | ==[[11β-hydroxylase deficiency epidemiology and demographics|Epidemiology and Demographics]]== |
| Because 11β-hydroxylase activity is not necessary in the production of [[sex steroid]]s ([[androgen]]s and [[estrogen]]s), the hyperplastic adrenal cortex produces excessive amounts of [[DHEA]], [[androstenedione]], and especially [[testosterone]].
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| These [[androgen]]s produce effects that are similar to those of [[congenital adrenal hyperplasia|21-hydroxylase deficient CAH]]. In the severe forms, XX (genetically female) fetuses can be markedly virilized, with [[ambiguous genitalia]] that look more male than female, though internal female organs, including [[ovary|ovaries]] and [[uterus]] develop normally.
| | ==[[11β-hydroxylase deficiency risk factors|Risk Factors]]== |
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| XY fetuses (genetic males) typically show no signs of excess androgens.
| | ==[[11β-hydroxylase deficiency screening|Screening]]== |
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| In milder mutations, androgen effects in both sexes appear in mid-childhood as early pubic hair, overgrowth, and accelerated bone age. Although "nonclassic" forms causing hirsutism and menstrual irregularities and appropriate steroid elevations have been reported, most have not had verifiable mutations and mild 11β-hydroxylase deficient CAH is currently considered a very rare cause of hirsutism and infertility.
| | ==[[11β-hydroxylase deficiency natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| All of the issues related to virilization, neonatal assignment, advantages and disadvantages of genital surgery, childhood and adult virilization, gender identity and sexual orientation are similar to those of 21-hydroxylase CAH and elaborated in more detail in [[Congenital adrenal hyperplasia]].
| | ==Diagnosis== |
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| | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency history and symptoms|History and Symptoms]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency physical examination|Physical Examination]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency laboratory findings|Laboratory Findings]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency CT|CT]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency MRI|MRI]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency ultrasound|Ultrasound]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency other imaging findings|Other Imaging Findings]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency other diagnostic studies|Other Diagnostic Studies]] |
| ===Management of 11β-hydroxylase deficient CAH===
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| As with other forms of CAH, the primary therapy of 11β-hydroxylase deficient CAH is life-long [[glucocorticoid]] replacement in sufficient doses to prevent [[adrenal insufficiency]] and suppress excess mineralocorticoid and androgen production.
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| Salt-wasting in infancy responds to intravenous saline, dextrose, and high dose [[hydrocortisone]], but prolonged [[fludrocortisone]] replacement is usually not necessary. The hypertension is ameliorated by glucocorticoid suppression of DOC.
| | ==Treatment== |
| | | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency medical therapy|Medical Therapy]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency surgery|Surgery]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency prevention|Prevention]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency future or investigational therapies|Future or Investigational Therapies]] |
| Long term [[glucocorticoid]] replacement issues are similar to those of [[congenital adrenal hyperplasia|21-hydroxylase CAH]], and involve careful balance between doses sufficient to suppress androgens while avoiding suppression of growth. Because the enzyme defect does not affect [[sex steroid]] synthesis, gonadal function at puberty and long-term fertility should be normal if adrenal androgen production is controlled. See [[congenital adrenal hyperplasia]] for a more detailed discussion of androgen suppression and fertility potential in adolescent and adult women.
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| ==See also== | |
| *[[Congenital adrenal hyperplasia]] for an overview of CAH, and a more detailed discussion of management issues related to the common forms of 21-hydroxylase deficiency. Nearly all of the sex steroid-related issues are the same for both 11β-hydroxylase and 21-hydroxylase deficient CAH.
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| *[[Lipoid congenital adrenal hyperplasia]]
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| *[[Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency|Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency]]
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| *[[Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency|Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency]]
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| *[[Intersex]] and [[ambiguous genitalia]]
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| *[[Adrenal insufficiency]]
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| [[Category:Pediatrics]]
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| [[Category:Endocrinology]]
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| [[Category:Genetic disorders]]
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| [[Category:Intersexuality]]
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