Virilizing congenital adrenal hyperplasia
Endocrinology / / May 01, 2016
virilizing congenital adrenal hyperplasia cortex - a disease in which due to the violation of hormone synthesis in the adrenal cortex in the blood to an excessive amount of steroids with androgenic action.The main manifestations of the disease are associated with virilizing and anabolic effects of hormonally active substances.Moreover, in some forms of the disease it is important lowering cortisol release adrenal cortex, as well as in the blood delivery of bioactive steroids, in physiological conditions, the adrenals do not secreted or secreted in a small amount.
first description of a patient with the presence of male secondary sexual characteristics, which increase the bilateral adrenal glands were found at autopsy, given in 1865 Crechio.
Subsequently, a number of researchers has established a relationship of some forms virilism in women and girls and precocious puberty in boys from violations of adrenal function.However, the nature of the disease, and hormonal disorders, under
In 1950, Wilkins et al.We proposed an effective method of treatment of congenital virilizing hyperplasia cortisone.
The etiology of the disease the most important seems to be playing a genetic factor.The deficiency of certain enzyme systems in the adrenal glands is innate.The value of the genetic factor is confirmed by numerous descriptions of cases the representatives of one family.In addition, hormonal studies in relatives of patients with congenital virilizing adrenal hyperplasia, who had no clinical manifestations of the disease, revealed in some cases, biochemical changes indicative of a weak degree of impairment of steroidogenesis in the same type as in patients.
Pathogenesis The pathogenesis of the disease is a violation of enzyme systems in the adrenal cortex, which leads to insufficient production of cortisol.The consequence of this is to reduce the inhibitory effect of corticosteroids in the anterior pituitary.Isolation of ACTH by the anterior pituitary increases.Increased adrenal ACTH stimulation leads, on the one hand, to the fact that cortisol production, despite the violation of its synthesis, the majority of patients reach a level that ensures the organism needs.On the other hand, those steroids which synthesis is not disturbed, in particular 17-keto steroids having androgenic effect produced and enter the blood in an excessive amount.In addition, overstimulation and the adrenal steroidogenesis in these disorders may cause blood to enter the deoxycorticosterone and possibly some steroids, not normally produced by the adrenal glands.
In Bartter ideas et al., Shared by most authors, an excess of androgens leads to abnormal development of the sexual organs of female fetuses, the appearance of male secondary sexual characteristics in girls and women, and premature sexual development in boys.Because of the inhibitory effect of androgens on the gonadotropic pituitary function under this scheme, their own sex glands in individuals, both male and female are underdeveloped and gipofunktsioniruyuschimi that appears uterine hypoplasia, absence of menstrual periods, and underdevelopment of the breast in women and testicular atrophy in men.
idea of insufficiency of cortisol production as the primary link in the pathogenesis of the disease has been confirmed by studies showing that children with congenital adrenal hyperplasia 17-gidroksikortikosteroidov content in the blood is reduced.It was also found that administration to patients of congenital virilizing hyperplasia ACTH adrenal cortex leads to increased isolation 17-keto steroids, but not 17-gidroksikortikosteroidov, indicating a violation of their synthesis.Insufficient production of cortisol, apparently, may depend on the irregularities in various enzyme systems.The greatest importance is attached to a breach of C21-hydroxylation.
Degree violation C21-hydroxylation may be different, and the majority of patients as a result of increased stimulation of the adrenal cortex, cortisol is produced in an amount sufficient to provide the body's needs.Aldosterone synthesis unit in this form of the enzyme systems generally do not disturbed and may even be increased.
younger children often (1 / 3-1 / 6 of all cases of congenital virilizing adrenal hyperplasia), there is increased excretion of sodium in urine, accompanied by dehydration, low blood pressure - the so-called salt loss syndrome.This syndrome in some cases may be associated with a decrease in aldosterone production.However described, and such patients with the syndrome of salt loss, in which the restriction of sodium in the diet led to an increase in release of aldosterone, but not accompanied by an increase in sodium retention.sodium loss in these cases may be attributed to the blood entering gidroksiprogesteroia 17 having the ability to promote sodium excretion or any other steroid with similar properties.Of great importance in the pathogenesis of salt loss syndrome is also attached to a sharp deficiency of cortisol.
more rare form of violation of enzyme systems is more or less complete blockade of hydroxylation at the C11 carbon atom.This increases the production of 11-deoxycortisol having small, biological effects, and 11-deoxycorticosterone, which is active mineralocorticoid.There has been increasing isolation in the urine.20-and 20-ketopregnantriola ketopregnandiola (metabolite MLC).Clinically, in this form of the disease, along with virilization, marked increase in blood pressure.
Even more rare is the blockade of the enzyme systems in the level of education earlier predecessors corticosteroids - 5-pregnenolone.At the same time there is a total failure of the adrenal cortex associated with impaired formation of glycol and mineralocorticoid that usually leads to death of patients at an early age.
notion that patients with congenital virilizing adrenal hyperplasia due to insufficient production of cortisol disinhibited adrenocorticotropic pituitary function, confirm hormonal studies, which revealed in these patients increased amounts of adrenocorticotropic hormone in the blood.
Inhibition of sexual development at izoseksualnomu type in women, according to the ideas of many authors, due to the inhibitory effect of androgens on the large number of gonadotropic pituitary function.However, there are reasons to believe that in this case the most important is the antagonistic action of androgens relative to estrogens at the tissue level.
Pathological changes in the adrenal glands are expressed primarily in their considerable hypertrophy.adrenal weight in the dead can reach 80-90, the most pronounced hyperplasia of reticular zone, while the beam zone - normal or even reduced.Glomerular zone in various observations were either normal or hyperplastic, and in some cases - children with a syndrome of loss of salt - was absent.Describes cases of congenital virilizing adrenal hyperplasia with cortical hyperplasia all three zones and a plurality of giant cells, particularly in the area of the beam;such cells are often found in malignant tumors of adrenal and embryos.
Various types of changes were observed in the gonads.Describes ovarian atrophy with a complete lack of primordial follicles and atresial.Along with this, other observations detected changes in the type of ovarian sclerocystic ovaries with many small cysts, and thickening of the tunica.In men, there may be atrophy of the testes with the inhibition of spermatogenesis and the absence of interstitial cells, and - at least - the normal development of the testes.In some cases, there is a sharp aberrant adrenal hyperplasia tissue in the testes in boys.
Anatomical changes of female genital mutilation depend on the period in which manifests a pronounced effect of androgens.With the development of the disease in the early stages of intrauterine life period occurs urogenital sinus - the vagina and urethra open one hole, a marked hypertrophy of the clitoris.For those patients in whom the effect of androgens on sexual system manifests itself in the later stages of development, there is a greater or lesser degree of hypertrophy of the clitoris.The uterus is always sharply atrophic.It should be noted that even at extreme degrees of violations of women's genitalia is always a vagina and uterus, so that the restoration of the normal structure of the genital organs requires only a limited and relatively simple surgery.
In boys, there are varying degrees of hypertrophy of the penis.
disease Severe congenital virilizing adrenal hyperplasia - an infrequent disease.Include numbers - 1 case of congenital virilizing adrenal hyperplasia in the 67-70 thousand births.However, in later years, when the diagnosis of diseases has improved, it presents data indicating a greater incidence of disease - 1 case per 5041 birth.If we take into account that in many patients symptoms of the disease at birth are mild and symptoms of dysfunction of the adrenal cortex appear at an older age, the number of patients with severe congenital adrenal hyperplasia, appears to be much greater.Even more often less pronounced - erased form of the disease, which manifest themselves in adolescence or poslepubertatnom period in women mild symptoms of overproduction of androgens - a violation of the menstrual cycle, occurrence of hypertrichosis, acne.
In females the disease is described more often than men.According to Wilkins data from 119 patients they observed were only 29 boys.However, it should be borne in mind that when expressed forms of mild clinical diagnosis of the disease in its early age in boys may be difficult, and the manifestation of the disease at the age of close to puberty, practically impossible.
Clinical manifestations of disease are determined primarily by the metabolic action of androgens in excess produced by the adrenal cortex, less symptoms associated with insufficient production of glucocorticoid and possibly mineralocorticoid and secretion of adrenal steroids is not normally received inblood in any significant quantities.
Depending on the availability of certain violations are four main forms of the disease:
1) virilnoe form, is characterized by symptoms that depend on the metabolic action of androgens without visible manifestations of failure glucocorticoid and mineralocorticoid;
2) salt loss syndrome, in which along with virilization symptoms are dependent on the insufficient production of glucocorticoid and possibly mineralocorticoid or adrenal glands produce "solteryayuschego" steroid;
3) hypertensive form, which manifests itself, in addition to virilization symptoms associated with the arrival of the blood-dezoksikor tikosterona;
4) form of congenital virilizing adrenal hyperplasia with periodic fever associated with an increased inflow into the blood etioholanolona.
The most common form of the disease simple virility, at least - salt loss syndrome (37 patients of the software) and hypertensive form (8 of the software).There are only a few case reports of congenital virilizing adrenal hyperplasia with periodic fever.
When virility form virilizing congenital adrenal hyperplasia in females clinical manifestations of the disease largely depends on the age at which production of androgens by the adrenal glands start to exceed the normal level.If androgen overproduction took place in the early stages of fetal development -.. Before the end of the formation of the female genital organs, ie, up to 20 weeks of fetal development, the girls are born with a different kind of anomalies of the external genitalia.In extreme degrees of violations hypertrophied clitoris advanced foreskin may resemble the male penis, skrotolabialnye folds grow together, form a formation resembling a scrotum with a median suture.The urethra and vagina open a slit-like or circular opening at the base of the clitoris.It describes some cases where the urethra is held in the interior of the clitoris.Such malformations of the external genitalia, in some cases give rise to misinterpretation of the sex of the baby at birth.The internal genitals of girls differentiate correctly.
If androgenic effect of in utero were less pronounced or appeared in the later stages of development, when the formation of the reproductive system is mainly over, abnormal development of the external genitalia may be limited only to a greater or lesser degree of hypertrophy of the clitoris, vagina and urethra are opened separately.
In some patients with impaired function of the adrenal cortex with increased androgen production occurs only after birth.In these cases, girls are born with normally developed sexual organs.
In childhood, androgen excess is manifested primarily anabolic effect - the rapid growth of the child, strengthening the development of muscles, increased muscle strength, the accelerated maturation of the skeleton.Build approaching male - there is increased development of the shoulder girdle with a relatively narrow pelvis.
Figure: virilizing congenital adrenal hyperplasia.The patient was 12 years old.
same reason, which leads to accelerated growth, anabolic effects of androgens causes and premature ossification of the epiphyseal cartilage and consequently - the cessation of growth.Therefore, children under a certain age overtaking in the growth and physical development of their peers, due to the shorter duration of the period of growth are relatively undersized.
in early childhood can manifest themselves and symptoms associated with virilizing effect of androgens.Appears vegetation pubic and axillary areas progresses hypertrophy of the clitoris, larynx assumes a structure peculiar to men, dropping his voice, there are acne, more or less pronounced hypertrichosis.In connection with the increased production of adrenocorticotropic hormone or melanoforotropnogo factor in many patients observed pigmentation resembling pigmentation in chronic adrenal insufficiency.
During puberty and in adult women is not the development of the mammary glands, the uterus is in a state of atrophy.The most common - people of small stature with a male skeletal development and muscle hypertrophy, although some patients constitution approaching asthenic.
in adult female patients sometimes appears male-pattern baldness.Often patients appear early increased sexual desire that may be associated with virilizing effect of androgens.
with less pronounced violation steroidogenesis production of adrenal androgens can significantly increase only in adolescence or even after it.Despite the development of the disease in a relatively late age, it must be regarded as an inherent since it is based on the same congenital adrenal disorders in enzyme systems, as in the typical forms.
With the development of the erased forms of violations of the functions of the adrenal cortex with impaired steroidogenesis by the type of congenital virilizing adrenal hyperplasia puberty or poslepubertatnom period the main manifestations of the disease are irregular menstruation (gipooligomenoreya) and hypertrichosis.Young women often observed sterility.Some patients have a more or less hypertrophy of the clitoris, uterus hypoplasia, sometimes - underdevelopment of the mammary glands.