11β-hydroxylase deficiency overview: Difference between revisions
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Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency arises due to a defect in the [[gene]] encoding the [[enzyme]] steroid 11β-hydroxylase which mediates the final step of [[cortisol]] synthesis in the [[adrenal gland|adrenal]]. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated steroids. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may be classified according to clinical presentation into 2 subtypes: classic form and the non-classic form. Mutations in the ''CYP11B1'' gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as [[adrenal crisis]], [[conn syndrome]], [[gastric outlet obstruction]], [[congenital adrenal hyperplasia due to 17-hydroxylase deficiency]], [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency]], [[hypertension]], [[hypokalemia]], [[hypomagnesemia]], [[infertility]], [[polycystic ovarian syndrome]], [[malignant hypertension]], [[Stein-Leventhal syndrome]], and [[viral gastroenteritis]]. The prevalence of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is approximately 1 per 100,000 individuals the United States. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency affects male and female equally. The most potent risk factor in the development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the presence of [[family history]] of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Prenatal screening for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency by injection a dose of 11-deoxycortisol into the [[amniotic fluid]] is recommended for patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. If left untreated, patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include [[muscle weakness]], [[metabolic alkalosis]], and [[azoospermia]]. [[Prognosis]] is generally good with treatment. On abdominal [[CT scan]], congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]]. On abdominal [[MRI]], congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]]. Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates [[hyperplasia]], poorly defined zonation, and intermingling of the [[chromaffin]] and cortical cells. The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy. The predominant therapy for ambiguous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the surgical correction. | Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency arises due to a defect in the [[gene]] encoding the [[enzyme]] steroid 11β-hydroxylase which mediates the final step of [[cortisol]] synthesis in the [[adrenal gland|adrenal]]. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated steroids. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may be classified according to clinical presentation into 2 subtypes: classic form and the non-classic form. Mutations in the ''CYP11B1'' gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as [[adrenal crisis]], [[conn syndrome]], [[gastric outlet obstruction]], [[congenital adrenal hyperplasia due to 17-hydroxylase deficiency]], [[congenital adrenal hyperplasia due to 21-hydroxylase deficiency]], [[hypertension]], [[hypokalemia]], [[hypomagnesemia]], [[infertility]], [[polycystic ovarian syndrome]], [[malignant hypertension]], [[Stein-Leventhal syndrome]], and [[viral gastroenteritis]]. The prevalence of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is approximately 1 per 100,000 individuals the United States. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency affects male and female equally. The most potent risk factor in the development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the presence of [[family history]] of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Prenatal screening for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency by injection a dose of 11-deoxycortisol into the [[amniotic fluid]] is recommended for patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. If left untreated, patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include [[muscle weakness]], [[metabolic alkalosis]], and [[azoospermia]]. [[Prognosis]] is generally good with treatment. On abdominal [[CT scan]], congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]]. On abdominal [[MRI]], congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]]. Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates [[hyperplasia]], poorly defined zonation, and intermingling of the [[chromaffin]] and cortical cells. The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy. The predominant therapy for ambiguous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the surgical correction. | ||
==Historical Perspective== | ==Historical Perspective== | ||
11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated [[steroids]]. In 1999, White was the first to discover the association between homozygous [[mutation]] in the [[CYP11B1]] [[gene]] and development of 11β-hydroxylase deficiency. | |||
==Classification== | ==Classification== | ||
11β-hydroxylase deficiency may be classified according to the clinical presentation into 2 subtypes: the classic form and the non-classic form of the 11β-hydroxylase deficiency. | |||
==Pathophysiology== | ==Pathophysiology== | ||
11β-Hydroxylase deficiency is a type of [[congenital adrenal hyperplasia]] resulting from a defect in [[CYP11B1]] on [[chromosome 8]]. [[CYP11B1]] [[gene]] encodes an enzyme called [[11β-hydroxylase]] in the path of [[steroid biosynthesis]]. This enzyme is located in the zona fasciculate, and converts [[Deoxycortisol|11-deoxycortisol]] to [[cortisol]] and [[11-deoxycorticosterone]]. Lack of [[11β-hydroxylase]] enzyme in different amounts results in accumulation of [[Deoxycortisol|11-deoxycortisol]], and decrease amounts of [[cortisol]] and [[11-deoxycorticosterone]]. There is an elevation of [[adrenocorticotropic hormone]] results in overproduction of [[11-deoxycorticosterone]] (DOC) by mid-childhood. [[11-deoxycorticosterone]] is a weak [[mineralocorticoid]], but because of high amounts in this disease can cause [[mineralocorticoid excess]] effects such as salt retention, volume expansion, and [[hypertension]]. Non-classic forms mostly doesn't have verifiable [[mutations]] and mild 11β-hydroxylase deficiency is currently considered a very rare cause of [[hirsutism]] and [[infertility]]. | |||
==Causes== | ==Causes== | ||
Mutations in the ''CYP11B1'' gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. | Mutations in the ''CYP11B1'' gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. | ||
Revision as of 20:36, 2 August 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency arises due to a defect in the gene encoding the enzyme steroid 11β-hydroxylase which mediates the final step of cortisol synthesis in the adrenal. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated steroids. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may be classified according to clinical presentation into 2 subtypes: classic form and the non-classic form. Mutations in the CYP11B1 gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as adrenal crisis, conn syndrome, gastric outlet obstruction, congenital adrenal hyperplasia due to 17-hydroxylase deficiency, congenital adrenal hyperplasia due to 21-hydroxylase deficiency, hypertension, hypokalemia, hypomagnesemia, infertility, polycystic ovarian syndrome, malignant hypertension, Stein-Leventhal syndrome, and viral gastroenteritis. The prevalence of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is approximately 1 per 100,000 individuals the United States. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency affects male and female equally. The most potent risk factor in the development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the presence of family history of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Prenatal screening for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency by injection a dose of 11-deoxycortisol into the amniotic fluid is recommended for patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. If left untreated, patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include muscle weakness, metabolic alkalosis, and azoospermia. Prognosis is generally good with treatment. On abdominal CT scan, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands. On abdominal MRI, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands. Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates hyperplasia, poorly defined zonation, and intermingling of the chromaffin and cortical cells. The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy. The predominant therapy for ambiguous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the surgical correction.
Historical Perspective
11β-hydroxylase deficiency was first described by Dr. Walter Eberlein and Dr. Alfred M. Bongiovanni, American physicians, in 1956 based on the study they conducted on accumulated steroids. In 1999, White was the first to discover the association between homozygous mutation in the CYP11B1 gene and development of 11β-hydroxylase deficiency.
Classification
11β-hydroxylase deficiency may be classified according to the clinical presentation into 2 subtypes: the classic form and the non-classic form of the 11β-hydroxylase deficiency.
Pathophysiology
11β-Hydroxylase deficiency is a type of congenital adrenal hyperplasia resulting from a defect in CYP11B1 on chromosome 8. CYP11B1 gene encodes an enzyme called 11β-hydroxylase in the path of steroid biosynthesis. This enzyme is located in the zona fasciculate, and converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone. Lack of 11β-hydroxylase enzyme in different amounts results in accumulation of 11-deoxycortisol, and decrease amounts of cortisol and 11-deoxycorticosterone. There is an elevation of adrenocorticotropic hormone results in overproduction of 11-deoxycorticosterone (DOC) by mid-childhood. 11-deoxycorticosterone is a weak mineralocorticoid, but because of high amounts in this disease can cause mineralocorticoid excess effects such as salt retention, volume expansion, and hypertension. Non-classic forms mostly doesn't have verifiable mutations and mild 11β-hydroxylase deficiency is currently considered a very rare cause of hirsutism and infertility.
Causes
Mutations in the CYP11B1 gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.
Differentiating Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency from other Diseases
Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as adrenal crisis, conn syndrome, gastric outlet obstruction, congenital adrenal hyperplasia due to 17-hydroxylase deficiency, congenital adrenal hyperplasia due to 21-hydroxylase deficiency, hypertension, hypokalemia, hypomagnesemia, infertility, polycystic ovarian syndrome, malignant hypertension, Stein-Leventhal syndrome, and viral gastroenteritis.
Epidemiology and Demographics
The prevalence of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is approximately 1 per 100,000 individuals the United States. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency affects male and female equally. Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency usually affects individuals of the Jewish race.
Risk Factors
The most potent risk factor in the development of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the presence of family history of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.
Screening
Prenatal screening for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency by injection a dose of 11-deoxycortisol into the amniotic fluid is recommended for patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.
Natural history, Complications and Prognosis
If left untreated, patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include muscle weakness, metabolic alkalosis, and azoospermia. Prognosis is generally good with treatment.
History and Symptoms
Symptoms of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include acne, oligomenorrhea, and aggressive behavior.
Physical Examination
Patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency usually appear healthy. Physical examination of patients with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is usually remarkable for gynaecomastia, hyperpigmentation, hypertension, and ambiguous genitalia.
Laboratory Findings
Laboratory findings consistent with the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include elevated 17α-hydroxyprogesterone, elevated androstenedione, elevated urinary 17-ketosteroids and decreased renin.
CT
On abdominal CT scan, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands.
MRI
On abdominal MRI, congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the adrenal glands.
Ultrasound
Ultrasound may be helpful in the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Findings on ultrasound suggestive of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency include testicular masses, adnexal structures, and gonadal abnormalities.
Other Imaging Findings
Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates hyperplasia, poorly defined zonation, and intermingling of the chromaffin and cortical cells.
Other Diagnostic Studies
Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency and it demonstrates hyperplasia, poorly defined zonation, and intermingling of the chromaffin and cortical cells.
Medical Therapy
The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy.
Surgery
The predominant therapy for ambiguous genitalia in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is the surgical correction.
Prevention
Prenatal diagnosis of 11-beta-hydroxylase deficiency is conducted to prevent the complication of the disease in future life and treated with prenatal dexamethasone treatment.