17 alpha-hydroxylase deficiency

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

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.

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 may be classified into two types, based on severity and clinical findings: partial and severe form.

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 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.

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.

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

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.

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.

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

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

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

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

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.

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. Reconstructive surgery for ambiguous genitalia in genetically male patients may be advised.

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. 

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2], Ammu Susheela, M.D. [3]

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

• Congenital adrenal hyperplasia was first discovered by Dr. Luigi DeCrecchio, an Italian pathologist, in 1865 following a case report of a patient with enlarged adrenal glands, male external genitalia, absence of testicles, and female internal reproductive organs.
• In 1963 congenital adrenal hyperplasia is categorized as several closely related disorders, each caused by different enzyme abnormalities.^[1]
• 17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report.^[2]

• In 1963 congenital adrenal hyperplasia was categorized as several closely related disorders, each caused by different enzyme abnormalities.
• In 1965, the diagnostic approach of congenital adrenal hyperplasia was established by measuring the levels of adrenal hormones in the amniotic fluid.
• in 1966, the hallmark symptoms of 17 alpha-hydroxylase deficiency (17OHD) was first described.
• In 1982, International Newborn Screening Meeting recommended new born screening for congenital adrenal hyperplasia.^[3][2][4]

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

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.

• CYP17A1 gene defects can cause two type of enzyme deficiencies: 17α-hydroxylase enzyme deficiency and 17,20-lyase deficiency. The dual activities mediate key transformations in cortisol and sex steroid synthesis:
  • 17α-hydroxylase mediates the pathway: pregnenolone → 17-hydroxypregnenolone, also progesterone → 17-hydroxyprogesterone.
  • 17,20-lyase mediates pathway 17-hydroxypregnenolone → Dehydroepiandrosterone, also 17-hydroxyprogesterone → androstenedione.
• Mineralocorticoid excess is the major clinical clue distinguishing the 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids.
• In 17 alpha-hydroxylase deficiency, steroid biosynthesis will be limited to progesterone, 11-deoxycorticosterone (DOC), and corticosterone.
• 11-deoxycorticosterone (DOC) binds to the mineralocorticoid receptor and its excess amounts in 17 alpha-hydroxylase deficiency causes aldosterone effects such as volume expansion, hypertension, and hypokalemia. Also, 11-deoxycorticosterone (DOC) effects will suppress renin and aldosterone production.
• The most important features of 17 alpha-hydroxylase deficiency include hypertension, hypokalemia and sexual infantilism.
  • Hypertension and hypokalemia result from accumulation of cortisol precursors, that have mineralocorticoid characteristics.
  • Sexual infantilism results from the inability of adrenal cortex to synthesize androgens and estrogens.^{[1][2][3][4][5]}

• 17 alpha-hydroxylase deficiency is an inherited disease with an autosomal recessive pattern, which means both copies of the gene in each cell have gene mutations.
• Commonly, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.^[7]

• Ambiguous genitalia
• Hypertension

Gross pathology findings in patients with 17 alpha-hydroxylase deficiency are:^[8][9]

• Enlarged adrenal glands
• Wrinkled surface adrenal glands
• Cerebriform pattern adrenal glands (pathognomonic sign)
• Normal ultrasound appearances may also be seen
• Testicular masses may be identified representing adrenal rest tissue

In 17 alpha-hydroxylase deficiency microscopic findings may include:

• Diffuse cortical hyperplasia with smaller cells
• The cell cytoplasm can be vacuolated, and often more basophilic
• Rare mitotic figures may be present
• The hyperplastic cells typically lack features of cellular atypia^[10]

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

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

Mutations in the CYP17A1 gene cause 17 alpha-hydroxylase deficiency. This gene is located on chromosome 10.^[1]

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

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.

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. .^{[1][2][3][4][5][6][7][8]}

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

17 alpha-hydroxylase deficiency is a rare disease and from 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.

• 17 alpha-hydroxylase deficiency is a rare disease.
• Since 2010, only 130 individuals with severe, confirmed disease had been documented.^[1]

• Worldwide incidence of 17 alpha-hydroxylase deficiency is low, especially when compared with other forms of CAH.
• New cases of 17-hydroxylase deficiency continue to be reported.^[2]

• Patients of all age groups may develop 17 alpha-hydroxylase deficiency. The mean age of diagnosis is infancy and childhood.

• 17 alpha-hydroxylase deficiency affects male and female equally.

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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], Mehrian Jafarizade, M.D [3]

The most potent risk factor for the development of 17 alpha-hydroxylase deficiency is a positive family history of 17 alpha-hydroxylase deficiency.

The most potent risk factor for the development of 17 alpha-hydroxylase deficiency is a positive family history of 17 alpha-hydroxylase deficiency.^[1]

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

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

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

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2], Mehrian Jafarizade, M.D [3]

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.

If left untreated, patients with 17 alpha-hydroxylase deficiency may progress to develop malignant hypertension.

• Vascular hemorrhage
• Renal insufficiency
• Left ventricular hypertrophy
• Hypertensive retinopathy
• Stroke

• Muscle weakness
• Metabolic alkalosis
• Paralytic ileus

• Infertility

• The prognosis of 17 alpha-hydroxylase deficiency is generally good or excellent.