Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency
Encyclopedia
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia
resulting from a defect in the gene
for the enzyme
CYP17A1. It produces decreased synthesis of both cortisol
and sex steroid
s, with resulting increase in mineralocorticoid
production. Thus, common symptoms include mild hypocortisolism, ambiguous genitalia in genetic males or failure of the ovaries to function at puberty in genetic females, and hypertension
(respectively).
This form of CAH results from deficiency of the enzyme
17α-hydroxylase (also called CYP17A1). It accounts for less than 5% of the cases of congenital adrenal hyperplasia
and is inherited in an autosomal recessive manner with a reported incidence of about 1 in 50,000 births.
The most common abnormal allele
s of this condition impair both the 17α-hydroxylase activity and the 17,20-lyase activity of CYP17A1. Like other forms of CAH, 17α-hydroxylase deficiency impairs the efficiency of cortisol
synthesis, resulting in high levels of ACTH secretion and hyperplasia of the adrenal glands. Clinical effects of this condition include overproduction of mineralocorticoid
s and deficiency of prenatal and pubertal
sex steroid
s.
CYP17A1 functions in steroidogenesis, where it converts pregnenolone
and progesterone
to their 17-hydroxy forms. The enzyme itself is attached to the smooth endoplasmic reticulum
of the steroid-producing cells of the adrenal cortex
and gonad
s. CYP17A1 functions as both a 17α-hydroxylase and a 17,20-lyase. The dual activities mediate three key transformations in cortisol
and sex steroid
synthesis:
The hydroxylase reactions are part of the synthetic pathway to cortisol as well as sex steroids, but the lyase reaction is only necessary for sex steroid synthesis. Different alleles of the CYP17A1 gene result in enzyme molecules with a range of impaired or reduced function that produces a range of clinical problems. The OMIM number for diseases arising from mutations of this gene is 202110.
The dual enzyme activities were for many decades assumed to represent two entirely different genes and enzymes. Thus, medical textbooks and nosologies until quite recently described two different diseases: 17α-hydroxylase deficient CAH, and a distinct and even rarer defect of sex steroid synthesis termed 17,20-lyase deficiency (which is not a form of CAH). In the last decade it has become clearer that the two diseases are different forms of defects of the same gene. However, the clinical features of the two types of impairment are distinct enough that they are described separately in the following sections.
, and 18-deoxycorticosterone are elevated. Although these precursors of aldosterone
are weaker mineralocorticoids, the extreme elevations usually provide enough volume expansion, blood pressure elevation, and potassium depletion to suppress renin
and aldosterone production. Some persons with 17α-hydroxylase deficiency develop hypertension
in infancy, and nearly 90% do so by late childhood. The low-renin hypertension
is often accompanied by hypokalemia
due to urinary potassium wasting and metabolic alkalosis
. These features of mineralocorticoid excess are the major clinical clue distinguishig the more complete 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids. Treatment with glucocorticoid suppresses ACTH, returns mineralocorticoid production toward normal, and lowers blood pressure.
have enough weak glucocorticoid
activity to prevent glucocorticoid deficiency and adrenal crisis.
, neither the adrenals nor the ovaries can produce sex steroids, so neither breast development nor pubic hair appear. Investigation of delayed puberty yields elevated gonadotropin
s and normal karyotype, while imaging confirms the presence of ovaries and an infantile uterus. Discovery of hypertension and hypokalemic alkalosis
usually suggests the presence of one of the proximal forms of CAH, and the characteristic mineralocorticoid elevations confirm the specific diagnosis.
A few milder forms of this deficiency in genetic females have allowed relatively normal breast development and irregular menstruation. Evidence suggests that only 5% of normal enzyme activity may be enough to allow at least the physical changes of female puberty, if not ovulation
and fertility. In these girls, the elevated blood pressure was the primary clinical problem.
17α-Hydroxylase deficiency in genetic males (XY) results in moderate to severe reduction of fetal testosterone
production by both adrenals and testes. Undervirilization
is variable and sometimes complete. The appearance of the external genitalia ranges from normal female to ambiguous to mildly underdeveloped male. The most commonly described phenotype is a small phallus
, perineal
hypospadias
, small blind pseudovaginal pouch, and intra-abdominal or inguinal
testes. Wolffian duct
derivatives are hypoplastic or normal, depending on degree of testosterone deficiency. Some of those with partial virilization develop gynecomastia
at puberty even though masculinization is reduced. The presence of hypertension in the majority distinguishes them from other forms of partial androgen deficiency or insensitivity
. Fertility is impaired in those with more than minimal testoserone deficiency.
(e.g., DHEA) synthesis.
However, mineralocorticoid
(e.g., aldosterone) or glucocorticoid
(e.g., cortisol) levels remain normal.
Normal aldosterone level can be attributed to the fact that aldosterone is independent of hypothalamus-pituitary axis feedback system, being mainly controlled by the level of serum potassium. Because of the normal aldosterone level, hypertension is not expected.
Normal cortisol level can be explained by the strong negative feedback mechanism of cortisol on hypothalamus-pituitary axis system. That is, in the beginning, 17,20-lyase deficiency will block synthesis of sex steroid hormones, forcing the pathways to produce more cortisol. However, the initial excess of cortisol is rapidly corrected by negative feedback mechanism—high cortisol decreases secretion of adrenocorticotropic hormone (ACTH) from zona fasciculata of adrenal gland. Thus, there is no mineralocorticoid overproduction. Also, there is no adrenal hyperplasia.
It has also been observed in patients that the adrenocorticotropic hormone (ACTH) level remains in the normal range. The reason for this is still unclear.
The sex steroid deficiency produces effects similar to 17α-hydroxylase deficiency. Severely affected genetic females (XX) are born with normal internal and external genitalia and there are no clues to abnormality until adolescence, when both the androgenic and estrogenic signs (e.g., breasts and pubic hair) of puberty fail to occur. Gonadotropins are high and the uterus infantile in size. The ovaries may contain enlarged follicular cysts, and ovulation may not occur even after replacement of estrogen.
replacement, as in other forms of CAH.
Most genetic females with both forms of the deficiency will need replacement estrogen to induce puberty. Most will also need periodic progestin to regularize menses. Fertility is usually reduced because egg maturation and ovulation is poorly supported by the reduced intra-ovarian steroid production.
The most difficult management decisions are posed by the more ambiguous genetic (XY) males. Most who are severely undervirilized, looking more female than male, are raised as females with surgical removal of the nonfunctional testes. If raised as males, a brief course of testosterone can be given in infancy to induce growth of the penis. Surgery may be able to repair the hypospadias. The testes should be salvaged by orchiopexy
if possible. Testosterone must be replaced in order for puberty to occur and continued throughout adult life.
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
resulting from a defect in the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
CYP17A1. It produces decreased synthesis of both cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
and sex steroid
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
s, with resulting increase in mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
production. Thus, common symptoms include mild hypocortisolism, ambiguous genitalia in genetic males or failure of the ovaries to function at puberty in genetic females, and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
(respectively).
Pathophysiology
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
17α-hydroxylase (also called CYP17A1). It accounts for less than 5% of the cases of congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
and is inherited in an autosomal recessive manner with a reported incidence of about 1 in 50,000 births.
The most common abnormal allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s of this condition impair both the 17α-hydroxylase activity and the 17,20-lyase activity of CYP17A1. Like other forms of CAH, 17α-hydroxylase deficiency impairs the efficiency of cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
synthesis, resulting in high levels of ACTH secretion and hyperplasia of the adrenal glands. Clinical effects of this condition include overproduction of mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
s and deficiency of prenatal and pubertal
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
sex steroid
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
s.
CYP17A1 functions in steroidogenesis, where it converts pregnenolone
Pregnenolone
Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone sulfate is a GABAA antagonist and increases neurogenesis in the hippocampus.-Chemistry:Like other steroids,...
and progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
to their 17-hydroxy forms. The enzyme itself is attached to the smooth endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
of the steroid-producing cells of the adrenal cortex
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
and gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s. CYP17A1 functions as both a 17α-hydroxylase and a 17,20-lyase. The dual activities mediate three key transformations in cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
and sex steroid
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
synthesis:
- As 17α-hydroxylase it mediates pregnenolonePregnenolonePregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone sulfate is a GABAA antagonist and increases neurogenesis in the hippocampus.-Chemistry:Like other steroids,...
→ 17-hydroxypregnenolone17-Hydroxypregnenolone17-Hydroxypregnenolone , is a C21 steroid that is obtained by hydroxylation of pregnenolone at the C17α position. This step is performed by the mitochondrial cytochrome P450 enzyme 17α-hydroxylase that is present in the adrenal and gonads. Peak levels are reached in humans at the end of puberty... - and progesteroneProgesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
→ 17-hydroxyprogesterone17-Hydroxyprogesterone17-Hydroxyprogesterone is a C-21 steroid hormone produced during the synthesis of glucocorticoids and sex steroids.As a hormone, 17OHP also interacts with the progesterone receptor.-Production:...
. - As 17,20-lyase it mediates 17-hydroxypregnenolone → DHEA.
- An expected second 17,20-lyase reaction (17-hydroxyprogesterone → androstenedioneAndrostenedioneAndrostenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
) is mediated so inefficiently in humans as to be of no known significance.
The hydroxylase reactions are part of the synthetic pathway to cortisol as well as sex steroids, but the lyase reaction is only necessary for sex steroid synthesis. Different alleles of the CYP17A1 gene result in enzyme molecules with a range of impaired or reduced function that produces a range of clinical problems. The OMIM number for diseases arising from mutations of this gene is 202110.
The dual enzyme activities were for many decades assumed to represent two entirely different genes and enzymes. Thus, medical textbooks and nosologies until quite recently described two different diseases: 17α-hydroxylase deficient CAH, and a distinct and even rarer defect of sex steroid synthesis termed 17,20-lyase deficiency (which is not a form of CAH). In the last decade it has become clearer that the two diseases are different forms of defects of the same gene. However, the clinical features of the two types of impairment are distinct enough that they are described separately in the following sections.
Mineralocorticoid effects
The adrenal cortex is hyperplastic and overstimulated, with no impairment of the mineralocorticoid pathway. Consequently, levels of DOC, corticosteroneCorticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
, and 18-deoxycorticosterone are elevated. Although these precursors of aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
are weaker mineralocorticoids, the extreme elevations usually provide enough volume expansion, blood pressure elevation, and potassium depletion to suppress renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
and aldosterone production. Some persons with 17α-hydroxylase deficiency develop hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
in infancy, and nearly 90% do so by late childhood. The low-renin hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
is often accompanied by hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
due to urinary potassium wasting and metabolic alkalosis
Metabolic alkalosis
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*Alkalosis...
. These features of mineralocorticoid excess are the major clinical clue distinguishig the more complete 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids. Treatment with glucocorticoid suppresses ACTH, returns mineralocorticoid production toward normal, and lowers blood pressure.
Glucocorticoid effects
Although production of cortisol is inefficient enough to normalize ACTH, the 50-100-fold elevations of corticosteroneCorticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
have enough weak glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
activity to prevent glucocorticoid deficiency and adrenal crisis.
Sex steroid effects
Genetic XX females affected by 17α-hydroxylase deficiency are born with normal female internal and external anatomy. At the expected time of pubertyPuberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, neither the adrenals nor the ovaries can produce sex steroids, so neither breast development nor pubic hair appear. Investigation of delayed puberty yields elevated gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s and normal karyotype, while imaging confirms the presence of ovaries and an infantile uterus. Discovery of hypertension and hypokalemic alkalosis
Alkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...
usually suggests the presence of one of the proximal forms of CAH, and the characteristic mineralocorticoid elevations confirm the specific diagnosis.
A few milder forms of this deficiency in genetic females have allowed relatively normal breast development and irregular menstruation. Evidence suggests that only 5% of normal enzyme activity may be enough to allow at least the physical changes of female puberty, if not ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
and fertility. In these girls, the elevated blood pressure was the primary clinical problem.
17α-Hydroxylase deficiency in genetic males (XY) results in moderate to severe reduction of fetal testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
production by both adrenals and testes. Undervirilization
Virilization
In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
is variable and sometimes complete. The appearance of the external genitalia ranges from normal female to ambiguous to mildly underdeveloped male. The most commonly described phenotype is a small phallus
Phallus
A phallus is an erect penis, a penis-shaped object such as a dildo, or a mimetic image of an erect penis. Any object that symbolically resembles a penis may also be referred to as a phallus; however, such objects are more often referred to as being phallic...
, perineal
Perineum
In human anatomy, the perineum is a region of the body including the perineal body and surrounding structures...
hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
, small blind pseudovaginal pouch, and intra-abdominal or inguinal
Inguinal canal
The inguinal canal is a passage in the anterior abdominal wall which in men conveys the spermatic cord and in women the round ligament. The inguinal canal is larger and more prominent in men.-Site:...
testes. Wolffian duct
Wolffian duct
The mesonephric duct is a paired organ found in mammals including humans during embryogenesis....
derivatives are hypoplastic or normal, depending on degree of testosterone deficiency. Some of those with partial virilization develop gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
at puberty even though masculinization is reduced. The presence of hypertension in the majority distinguishes them from other forms of partial androgen deficiency or insensitivity
Androgen insensitivity syndrome
Androgen insensitivity syndrome is a condition that results in the partial or complete inability of the cell to respond to androgens. The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as...
. Fertility is impaired in those with more than minimal testoserone deficiency.
17,20-lyase deficiency
A very small number of people have reportedly had an abnormal allele that resulted primarily in a reduction of 17,20-lyase activity, rather than both the hydroxylase and lyase activities as described above. In these people the defect had the effect of an isolated impairment of sex steroidSex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
(e.g., DHEA) synthesis.
However, mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
(e.g., aldosterone) or glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
(e.g., cortisol) levels remain normal.
Normal aldosterone level can be attributed to the fact that aldosterone is independent of hypothalamus-pituitary axis feedback system, being mainly controlled by the level of serum potassium. Because of the normal aldosterone level, hypertension is not expected.
Normal cortisol level can be explained by the strong negative feedback mechanism of cortisol on hypothalamus-pituitary axis system. That is, in the beginning, 17,20-lyase deficiency will block synthesis of sex steroid hormones, forcing the pathways to produce more cortisol. However, the initial excess of cortisol is rapidly corrected by negative feedback mechanism—high cortisol decreases secretion of adrenocorticotropic hormone (ACTH) from zona fasciculata of adrenal gland. Thus, there is no mineralocorticoid overproduction. Also, there is no adrenal hyperplasia.
It has also been observed in patients that the adrenocorticotropic hormone (ACTH) level remains in the normal range. The reason for this is still unclear.
The sex steroid deficiency produces effects similar to 17α-hydroxylase deficiency. Severely affected genetic females (XX) are born with normal internal and external genitalia and there are no clues to abnormality until adolescence, when both the androgenic and estrogenic signs (e.g., breasts and pubic hair) of puberty fail to occur. Gonadotropins are high and the uterus infantile in size. The ovaries may contain enlarged follicular cysts, and ovulation may not occur even after replacement of estrogen.
Management
Hypertension and mineralocorticoid excess is treated with glucocorticoidGlucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
replacement, as in other forms of CAH.
Most genetic females with both forms of the deficiency will need replacement estrogen to induce puberty. Most will also need periodic progestin to regularize menses. Fertility is usually reduced because egg maturation and ovulation is poorly supported by the reduced intra-ovarian steroid production.
The most difficult management decisions are posed by the more ambiguous genetic (XY) males. Most who are severely undervirilized, looking more female than male, are raised as females with surgical removal of the nonfunctional testes. If raised as males, a brief course of testosterone can be given in infancy to induce growth of the penis. Surgery may be able to repair the hypospadias. The testes should be salvaged by orchiopexy
Orchiopexy
Orchiopexy is a surgery to move an undescended testicle into the scrotum and permanently fix it there. It is performed by a pediatric urologist or surgeon on boys with cryptorchidism, typically before they reach the age of two...
if possible. Testosterone must be replaced in order for puberty to occur and continued throughout adult life.
See also
- Congenital adrenal hyperplasiaCongenital adrenal hyperplasiaCongenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
for an overview of CAH, more detailed discussion of management issues related to all forms of CAH, and links to support groups. - Lipoid congenital adrenal hyperplasiaLipoid congenital adrenal hyperplasiaLipoid congenital adrenal hyperplasia is an endocrine disorder that is an uncommon and potentially lethal form of congenital adrenal hyperplasia...
- Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiencyCongenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency3β-Hydroxysteroid dehydrogenase II deficient congenital adrenal hyperplasia is an uncommon form of CAH resulting from a mutation in the gene for one of the key enzymes in cortisol synthesis by the adrenal gland, 3β-hydroxysteroid dehydrogenase type II...
- Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
- IntersexIntersexIntersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
and ambiguous genitalia - Adrenal insufficiencyAdrenal insufficiencyAdrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...