Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
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Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency | |
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Other names | CYP11B1 deficiency |
steroidogenesis . The action of 11β-hydroxylase is seen in red box at right. |
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a form of congenital adrenal hyperplasia (CAH) which produces a higher than normal amount of androgen,[1] resulting from a defect in the gene encoding the enzyme steroid 11β-hydroxylase (11β-OH) which mediates the final step of cortisol synthesis in the 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 virilize a genetically female fetus or a child of either sex.
Presentation
Mineralocorticoid effects
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.[2]
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 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.[2]
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
Sex steroid effects
Because
These
XY fetuses (genetic males) typically show no abnormal features related to androgen excess. A megalopenis (>22 cm/8.7in) is usually present in male patients.
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.
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.
Pathophysiology
The enzyme which mediates 11β-hydroxylase activity is now known as P450c11β since it is one of the
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.
Diagnosis
Classification
Congenital adrenal hyperplasia (CAH) refers to any of several
The most common type of CAH is due to 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-OH CAH resembles
Management
As with other forms of CAH, the primary therapy of 11β-hydroxylase deficient CAH is lifelong glucocorticoid replacement in sufficient doses to prevent adrenal insufficiency and suppress excess mineralocorticoid and androgen production.
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.
Long term
See also
- Inborn errors of steroid metabolism
- Congenital adrenal hyperplasia
- Adrenal insufficiency
- Disorders of sexual development
- ambiguous genitalia
- Steroid 11β-hydroxylase
References
- ^ "11-beta-hydroxylase deficiency | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2019-03-28. Retrieved 2017-08-18.
- ^ ISSN 1923-4163.