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{{Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency}}
{{17 alpha-hydroxylase deficiency}}
{{CMG}}; {{AE}} {{Ammu}}
{{CMG}}; {{AE}} {{MJ}}
==Overview==
==Overview==
Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report.<ref name="BiglieriHerron1966">{{cite journal|last1=Biglieri|first1=E G|last2=Herron|first2=M A|last3=Brust|first3=N|title=17-hydroxylation deficiency in man.|journal=Journal of Clinical Investigation|volume=45|issue=12|year=1966|pages=1946–1954|issn=0021-9738|doi=10.1172/JCI105499}}</ref>Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of [[congenital adrenal hyperplasia]] resulting from a defect in the [[gene]] [[CYP17A1]], which encodes for the [[enzyme]]  17α-hydroxylase. Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is transmitted in autosomal recessive pattern. ''CYP17A1'' gene mutation is involved in the pathogenesis of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. On gross pathology, thickening of the [[adrenal gland]] and cerebriform appearance are characteristic findings of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. On microscopic histopathological analysis, diffuse cortical hyperplasia and lipid-depleted cortical cells are characteristic findings of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. Mutations in the ''CYP17'' gene cause congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as 5-alpha-reductase deficiency and hypogonadism. If left untreated, patients with congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency may progress to develop [[malignant hypertension]]. Common complications of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency include muscle weakness, [[metabolic alkalosis]], and [[azoospermia]]. Prognosis is generally good with treatment. On abdominal [[CT scan]], congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]]. The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy. The predominant therapy for ambigous genitalia in congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is surgical correction.
17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American [[endocrinologist]], in 1963-1966 following publication of a case report. 17 alpha-hydroxylase deficiency is an uncommon form of [[congenital adrenal hyperplasia]] resulting from a defect in the [[gene]] [[CYP17A1]], which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an [[autosomal recessive]] pattern. [[Mineralocorticoid excess]] and lack of [[androgens]] are two main features in this disease. [[Mutations]] in the [[CYP17A1]] gene cause 17 alpha-hydroxylase deficiency. This gene is located on [[chromosome 10]]. 17 alpha-hydroxylase deficiency is a rare disease and since 2010, only 130 individuals with severe, confirmed disease had been documented. Worldwide [[incidence]] of 17 alpha-hydroxylase deficiency is low, especially compared with other forms of [[CAH]]. New cases of 17-hydroxylase deficiency continue to be reported. The most potent risk factor in the development of 17 alpha-hydroxylase deficiency is the presence of [[family history]] of 17 alpha-hydroxylase. Symptoms of 17 alpha-hydroxylase deficiency include [[delayed puberty]] and [[primary amenorrhea]]. Patients with 17 alpha-hydroxylase deficiency usually appear normal. Physical examination of patients with 17 alpha-hydroxylase deficiency is usually remarkable for [[gynaecomastia]], [[hypertension]], and [[sexual infantilism]]. Laboratory findings consistent with the diagnosis of 17 alpha-hydroxylase deficiency include increased [[deoxycorticosterone]] and [[corticosterone]] with low [[cortisol]]. The mainstay of therapy for 17 alpha-hydroxylase deficiency is [[glucocorticoid]] therapy. [[Spironolactone]] and [[Estrogen-replacement therapy|estrogen]] also may be used. Affected [[46,XY]] patients require gonadectomy to prevent [[malignant]] degeneration of [[testes]]. The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be considered.
 
==Historical Perspective==
==Historical Perspective==
Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report.<ref name="BiglieriHerron1966">{{cite journal|last1=Biglieri|first1=E G|last2=Herron|first2=M A|last3=Brust|first3=N|title=17-hydroxylation deficiency in man.|journal=Journal of Clinical Investigation|volume=45|issue=12|year=1966|pages=1946–1954|issn=0021-9738|doi=10.1172/JCI105499}}</ref>
17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American [[endocrinologist]], in 1963-1966 following publication of a case report.  
==Classification==
17 alpha-hydroxylase deficiency may be classified into two types, based on severity and clinical findings: partial and severe form.
 
==Pathophysiology==
==Pathophysiology==
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of [[congenital adrenal hyperplasia]] resulting from a defect in the [[gene]] [[CYP17A1]], which encodes for the [[enzyme]]  17α-hydroxylase. Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is transmitted in autosomal recessive pattern. ''CYP17A1'' gene mutation is involved in the pathogenesis of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. On gross pathology, thickening of the [[adrenal gland]] and cerebriform appearance are characteristic findings of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. On microscopic histopathological analysis, diffuse cortical hyperplasia and lipid-depleted cortical cells are characteristic findings of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency.
17 alpha-hydroxylase deficiency is an uncommon form of [[congenital adrenal hyperplasia]] resulting from a defect in the [[gene]] [[CYP17A1]], which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. [[Mineralocorticoid excess]] and lack of [[androgens]] are two main features in this disease.  
==Causes==
==Causes==
Mutations in the ''CYP17'' gene cause congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency.
[[Mutations]] in the [[CYP17A1]] [[gene]] cause 17 alpha-hydroxylase deficiency. This [[gene]] is located on [[chromosome 10]].  
==Differential Diagnosis==
==Differential Diagnosis==
Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency must be differentiated from other diseases that cause clinical features, such as 5-alpha-reductase deficiency and [[hypogonadism]].
17 alpha-hydroxylase deficiency must be differentiated from diseases that present with [[primary amenorrhea]] and female [[external genitalia]] such as [[pregnancy]], [[androgen insensitivity syndrome]], 3beta-hydroxysteroid dehydrogenase type 2 deficiency, [[gonadal dysgenesis]], [[testicular regression syndrome]], [[LH receptor]] defects, [[5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], primary [[ovarian]] insufficiency, [[hypogonadotropic hypogonadism]] and [[turner syndrome]].
 
==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidencee of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency in the United States is approximately 1 per 100,000 individuals. Patients of all age groups may develop congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. The mean age of diagnosis is infancy and childhood.
17 alpha-hydroxylase deficiency is a rare disease and since 2010, only 130 individuals with severe, confirmed disease had been documented. Worldwide [[incidence]] of 17 alpha-hydroxylase deficiency is low, especially compared with other forms of [[CAH]]. New cases of 17-hydroxylase deficiency continue to be reported.
 
==Risk Factors==
==Risk Factors==
The most potent risk factor in the development of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is the presence of [[family history]] of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency.
The most potent risk factor in the development of 17 alpha-hydroxylase deficiency is the presence of [[family history]] of 17 alpha-hydroxylase.
 
==Screening==
==Screening==
Prenatal screening for congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency by measuring adrenal steroids in the amniotic fluid and monitoring maternal urine steroid metabolite excretion.
There is insufficient evidence to recommend routine screening for 17 alpha-hydroxylase deficiency.
 
==Natural history, Complications and Prognosis==
==Natural history, Complications and Prognosis==
If left untreated, patients with congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency may progress to develop [[malignant hypertension]]. Common complications of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency include muscle weakness, [[metabolic alkalosis]], and [[azoospermia]]. Prognosis is generally good with treatment.
If left untreated, patients with 17 alpha-hydroxylase deficiency may progress to develop [[malignant hypertension]]. Common complications of 17 alpha-hydroxylase deficiency include [[muscle weakness]], [[metabolic alkalosis]], and [[infertility]]. Prognosis is generally good with treatment.
 
==History and Symptoms==
==History and Symptoms==
Symptoms of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency include delayed puberty and primary amenorrhea.<ref> Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Wikipedia (2016). https://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_11%CE%B2-hydroxylase_deficiency Accessed on January 29, 2016</ref>
Symptoms of 17 alpha-hydroxylase deficiency include [[delayed puberty]] and [[primary amenorrhea]].
 
==Physical Examination==
==Physical Examination==
Patients with congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency usually appear general appearance. Physical examination of patients with congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is usually remarkable for [[gynaecomastia]], [[hypertension]], and [[sexual infantilism]].
Patients with 17 alpha-hydroxylase deficiency usually appear normal. Physical examination of patients with 17 alpha-hydroxylase deficiency is usually remarkable for [[gynaecomastia]], [[hypertension]], and [[sexual infantilism]].
 
==Laboratory Findings==
==Laboratory Findings==
Laboratory findings consistent with the diagnosis of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency include elevated 17α-hydroxyprogesterone, elevated androstenedione, elevated urinary 17-ketosteroids and decreased renin.
Laboratory findings consistent with the diagnosis of 17 alpha-hydroxylase deficiency include increased [[deoxycorticosterone]] and [[corticosterone]] with low [[cortisol]].
 
==CT==
==CT==
On abdominal [[CT scan]], congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]].
Abdominal [[CT scan]] findings consistent with 17 alpha-hydroxylase deficiency includes bilateral symmetric enlargement of the [[adrenal glands]].
 
==MRI==
==MRI==
On abdominal [[MRI]], congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is characterized by bilateral symmetric enlargement of the [[adrenal glands]].
Abdominal [[MRI]] findings consistent with 17 alpha-hydroxylase deficiency includes bilateral symmetric enlargement of the [[adrenal glands]].
 
==Echocardiography or Ultrasound==
==Echocardiography or Ultrasound==
Ultrasound may be helpful in the diagnosis of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency.  
On [[ultrasound]], 17 alpha-hydroxylase deficiency is characterized by enlarged, wrinkled, and cerebriform [[adrenal glands]].
 
==Other Imaging Findings==
==Other Imaging Findings==
There is no other imaging studies available for the diagnosis of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency.
There are no other imaging studies available for the diagnosis of 17 alpha-hydroxylase deficiency.
 
==Other Diagnostic Studies==
==Other Diagnostic Studies==
Immunohistochemical staining of the adrenal gland may be used for the diagnosis of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency and it demonstrates [[hyperplasia]], poorly defined zonation, and intermingling of the [[chromaffin]] and cortical cells.
[[Prenatal diagnosis]] may be used in  the diagnosis of 17 alpha-hydroxylase deficiency. Different tests may be used such as [[amniotic fluid]] sampling and oligonucleotide [[hybridization]] of [[deoxyribonucleic acid]] ([[DNA]]) obtained from [[Chorionic villus sampling|chorionic villus biopsies]]; and utilize fetal [[DNA]] extracted from maternal blood through noninvasive methods.
 
==Medical Therapy==
==Medical Therapy==
The mainstay of therapy for congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is glucocorticoid therapy.
The mainstay of therapy for 17 alpha-hydroxylase deficiency is [[glucocorticoid]] therapy. [[Spironolactone]] and [[Estrogen-replacement therapy|estrogen]] also may be used.
 
==Surgery==
==Surgery==
The predominant therapy for ambigous genitalia in congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is surgical correction.
Affected [[46,XY|46, XY]] patients require gonadectomy to prevent [[malignant]] degeneration of [[testes]]. Reconstructive surgery for [[ambiguous genitalia]] in genetically male patients may be advised.
 
==Prevention==
==Prevention==
Prenatal diagnosis of 17 alpha-hydroxylase deficiency is conducted to prevent complication of the disease in future life and treated with prenatal dexamethasone treatment.
[[Prenatal diagnosis]] of 17 alpha-hydroxylase deficiency is advised in order to prevent complications of the disease further in life. [[Prenatal]] administration of [[dexamethasone]], which is the drug of choice helps prevent complications. 
 
==Reference==
==Reference==
{{Reflist}}
{{Reflist}}
[[Category:Disease]]
[[Category:Pediatrics]]
[[Category:Endocrinology]]
[[Category:Genetic disorders]]
[[Category:Intersexuality]]

Latest revision as of 15:58, 20 October 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

Overview

17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report. 17 alpha-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. Mineralocorticoid excess and lack of androgens are two main features in this disease. Mutations in the CYP17A1 gene cause 17 alpha-hydroxylase deficiency. This gene is located on chromosome 10. 17 alpha-hydroxylase deficiency is a rare disease and since 2010, only 130 individuals with severe, confirmed disease had been documented. Worldwide incidence of 17 alpha-hydroxylase deficiency is low, especially compared with other forms of CAH. New cases of 17-hydroxylase deficiency continue to be reported. The most potent risk factor in the development of 17 alpha-hydroxylase deficiency is the presence of family history of 17 alpha-hydroxylase. Symptoms of 17 alpha-hydroxylase deficiency include delayed puberty and primary amenorrhea. Patients with 17 alpha-hydroxylase deficiency usually appear normal. Physical examination of patients with 17 alpha-hydroxylase deficiency is usually remarkable for gynaecomastia, hypertension, and sexual infantilism. Laboratory findings consistent with the diagnosis of 17 alpha-hydroxylase deficiency include increased deoxycorticosterone and corticosterone with low cortisol. The mainstay of therapy for 17 alpha-hydroxylase deficiency is glucocorticoid therapy. Spironolactone and estrogen also may be used. Affected 46,XY patients require gonadectomy to prevent malignant degeneration of testes. The reconstruction surgery for ambiguous genitalia in genetically male patients may be considered.

Historical Perspective

17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report.

Classification

17 alpha-hydroxylase deficiency may be classified into two types, based on severity and clinical findings: partial and severe form.

Pathophysiology

17 alpha-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. Mineralocorticoid excess and lack of androgens are two main features in this disease.

Causes

Mutations in the CYP17A1 gene cause 17 alpha-hydroxylase deficiency. This gene is located on chromosome 10.

Differential Diagnosis

17 alpha-hydroxylase deficiency must be differentiated from diseases that present with primary amenorrhea and female external genitalia such as pregnancy, androgen insensitivity syndrome, 3beta-hydroxysteroid dehydrogenase type 2 deficiency, gonadal dysgenesis, testicular regression syndrome, LH receptor defects, 5-alpha-reductase type 2 deficiency, mullerian agenesis, primary ovarian insufficiency, hypogonadotropic hypogonadism and turner syndrome.

Epidemiology and Demographics

17 alpha-hydroxylase deficiency is a rare disease and since 2010, only 130 individuals with severe, confirmed disease had been documented. Worldwide incidence of 17 alpha-hydroxylase deficiency is low, especially compared with other forms of CAH. New cases of 17-hydroxylase deficiency continue to be reported.

Risk Factors

The most potent risk factor in the development of 17 alpha-hydroxylase deficiency is the presence of family history of 17 alpha-hydroxylase.

Screening

There is insufficient evidence to recommend routine screening for 17 alpha-hydroxylase deficiency.

Natural history, Complications and Prognosis

If left untreated, patients with 17 alpha-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of 17 alpha-hydroxylase deficiency include muscle weakness, metabolic alkalosis, and infertility. Prognosis is generally good with treatment.

History and Symptoms

Symptoms of 17 alpha-hydroxylase deficiency include delayed puberty and primary amenorrhea.

Physical Examination

Patients with 17 alpha-hydroxylase deficiency usually appear normal. Physical examination of patients with 17 alpha-hydroxylase deficiency is usually remarkable for gynaecomastia, hypertension, and sexual infantilism.

Laboratory Findings

Laboratory findings consistent with the diagnosis of 17 alpha-hydroxylase deficiency include increased deoxycorticosterone and corticosterone with low cortisol.

CT

Abdominal CT scan findings consistent with 17 alpha-hydroxylase deficiency includes bilateral symmetric enlargement of the adrenal glands.

MRI

Abdominal MRI findings consistent with 17 alpha-hydroxylase deficiency includes bilateral symmetric enlargement of the adrenal glands.

Echocardiography or Ultrasound

On ultrasound, 17 alpha-hydroxylase deficiency is characterized by enlarged, wrinkled, and cerebriform adrenal glands.

Other Imaging Findings

There are no other imaging studies available for the diagnosis of 17 alpha-hydroxylase deficiency.

Other Diagnostic Studies

Prenatal diagnosis may be used in the diagnosis of 17 alpha-hydroxylase deficiency. Different tests may be used such as amniotic fluid sampling and oligonucleotide hybridization of deoxyribonucleic acid (DNA) obtained from chorionic villus biopsies; and utilize fetal DNA extracted from maternal blood through noninvasive methods.

Medical Therapy

The mainstay of therapy for 17 alpha-hydroxylase deficiency is glucocorticoid therapy. Spironolactone and estrogen also may be used.

Surgery

Affected 46, XY patients require gonadectomy to prevent malignant degeneration of testes. Reconstructive surgery for ambiguous genitalia in genetically male patients may be advised.

Prevention

Prenatal diagnosis of 17 alpha-hydroxylase deficiency is advised in order to prevent complications of the disease further in life. Prenatal administration of dexamethasone, which is the drug of choice helps prevent complications. 

Reference