Gonadal dysgenesis ( Shereshevskii syndrome - Turner )
Endocrinology / / May 12, 2016
Diseases associated with impaired sexual differentiation
gonadal dysgenesis - a disease caused by a chromosomal abnormality and manifested a sharp violation of gonad development in the embryonic period, and often also various somatic abnormalities.
disease is based on the chromosomal anomaly.Most often, patients have one sex chromosome X (karyotype XO), often there is a mosaic type of XO / XX and XO / XY, often one of the X-chromosome is isochromosome, t. E. Consists of two long and two short arms instead of one longand one short (HH1 karyotype or XO / XX1).A number of patients have a karyotype XXX.Gonad calls for the development of the two sex chromosomes.Therefore, in patients with karyotype XO gonad does not develop and is a connective cord.If the karyotype XO / XX in the rudiments of the gonads may be a small number of immature follicular cells, while the karyotype XO / XY a certain number of the seminiferous tubules of immature cells and leydigovskie.Sometimes one gonad pr
Because patients usually do not have a testicular, and if there is one egg rudimentary, it does not produce embryonic hormones, internal reproductive organs develop on the female type, and patients have a uterus, tubes.Education androgen small, so the external genitalia develop on the female type.Only if the latter can leydigovskih cells produce sufficient amounts of androgens, which causes enlargement of the clitoris.In puberty does not occur in patients with feminization and menstruation occurs.If, however, in a rudimentary gonad develops tumor (gonotsitoma) to produce estrogen and androgens, may appear the phenomenon of feminization or virilization.
Maturation gonadotropin mechanisms occur in these patients is normal, and therefore in pubertal and post-pubertal age increased urine excretion of gonadotropins, and only in the development of hormonally active gonotsitomy reduced.
pathogenesis of somatic disorders in patients is unknown.Isolation of growth hormone is increased, but the increase in patients with low, suggesting vnegipofizarny mechanism of its delay.The origin of the heart and kidney malformations also unclear.
For every 10,000 live births, girls account for 12 patients with XXX karyotype (number of patients do not suffer from infertility) and 4 suffer from other sex chromosome abnormalities.Among patients with primary amenorrhea individuals with chromosomal abnormalities account for 40%.Family cases are extremely rare, so the presence of the family of one patient a second child with gonadal dysgenesis is highly unlikely.Age of parents do not play a role in determining the probability of occurrence in the family sick gonadal dysgenesis.
Clinic dysgenesis of the gonads is very diverse, but in most cases characterized by some common symptoms.
signs of the disease in newborns is lymphoedema dorsa, legs, and neck.A few months later the swelling takes place, and on the neck are loose folds of skin, reaching almost vertically from the occipital bone to the shoulder.In the 10-12 years it becomes noticeable lag in growth, although growth still continues for several years, but it slows down and stops in 17-20 years.By this age, patients generally have a growth of 130-145 cm, but sometimes more.(. See Figure 1, 2.)
Fig.1: Patient 18 years.
Figure 2: Patient 16 years.
There are irregularities in the structure of the metaphyses;epiphyseal closure slots usually does not happen.There have been high-quality skeletal anomalies - diffuse osteoporosis, shortening of IV metacarpal bone, cubitus, valgus, high hard palate, embedded in the bottom of the sternum of the body, etc. The neck is usually short, in conjunction with the skin folds gives often sick kind of sphinx (See...Fig. 3).
B Frequently there is a low hairline at the back of the neck, dark spots, abnormal development of ears, epicanthus, ptosis, telangiectasia.There are congenital malformations of the heart and large vessels (PFO or interventricular septum, coarctation of the aorta), and kidney malformations (horseshoe kidney, congenital absence of one kidney, pelvis and ureter anomaly and others.).
Patients suffer sexual infantilism - no menstruation, secondary body hair, breasts, there is a marked hypoplasia of the external genitalia and the uterus.At laparotomy patients found the uterus, tubes, ovaries but in place - a connective tissue bands, with serial sections which are sometimes found immature ovarian or testicular elements.
In many cases, the clinical picture is essential features.Patients with XXX karyotype is usually normal growth, puberty occurs puberty, menstruation can be regular, but usually disappear after a few years, and secondary amenorrhea occurs.In these patients, the ovaries at laparotomy look like those old women.At the same time with the same XXX karyotype and even XXXX karyotype described many patients with normal sexual development, had children.It should be emphasized that patients with XXX karyotype often marked mental retardation, while at the karyotype XO XO / XX, HH1 and others. Mental development is perfectly normal.
Significant changes in the clinical picture occur when a hormonally active tumor rudimentary gonads.If the tumor forms an estrogen, it comes feminization with the development of breast, uterine krovootdeleniyami and so on. D. With the development of tumors of the testicular cells, produce androgens, occurs virilization with hypertrophy of the clitoris, the appearance of hair growth in male pattern) (See. Fig. 4).
In some cases, the tumor existed for many years, and androgens secreted by it completely disfigured patients.Sometimes the tumor maligniziruetsya, and if it came from elements of the seminiferous tubules (seminoma), then pretty quickly metastasizes.In rare cases, the so-called "pure" gonadal dysgenesis in patients not observed any violations other than primary gonadal failure.The growth of normal patients, somatic abnormalities were observed.As can be seen, the clinical picture of the disease and karyotype are quite different.Common to all patients with gonadal dysgenesis is their primary failure.
Fig.3: Patient 18 years.
Fig.4: The patient was 27 years old.
From laboratory studies important data defines sex chromatin - at XO karyotype or XO / XY does not exist, when the karyotype XO / XX is available in a small number of cells (5-10% instead of 20-40% of the cells of buccal epithelium)at XXX karyotype it is unusually large or unusually small size, with the karyotype XXX celebrated the double chromatin.Studies karyotype often produced in a culture of skin cells or peripheral blood leukocytes, and bone marrow punctate.
Syndrome, reminding gonadal dysgenesis in women is described in boys.Such patients of low growth, with folds of skin on the neck, often with abnormalities of the skeleton and internal organs, usually with cryptorchidism.Histologically, the testes observed hypoplasia of the seminiferous tubules with a sharp violation of spermatogenic elements, and the number of cells leydigovskih normal, low or high.In all patients, there was no sex chromatin and karyotype was XY.
Diagnosis and differential diagnosis
The diagnosis is not difficult only in typical cases.From patients with pituitary dwarfism these patients have a higher growth, much less severe ossification delay, absence of phenomena of hypothyroidism;essential absence or change in the shape and frequency of sexual chromatin bodies, as well as detection of a large number of urinary gonadotropins (generally above 80-100 mg per day).When oligosymptomatic forms when patients increase within the normal range and there is no physical abnormalities, quite difficult differential diagnosis with other forms of primary ovarian insufficiency.In such cases, it is important to define sex chromatin and karyotype.At the same time it should be noted that the disease is not characteristic of any specific karyotype and sex chromosome abnormalities very different nature.
In cases where the patient has a feminization at diagnosis of gonadal dysgenesis, should think about the gonad tumors.The diagnosis is established only when the operation.
very difficult diagnosis in the case of testicular tumor cells, produce androgens.Such patients may be outwardly very reminding patients with congenital adrenal hyperplasia.The correct diagnosis can be set on the basis of normal or slightly increased discharge of urine 17-keto steroids, as well as the absence of sex chromatin.In these cases for further diagnosis laparotomy.
- Congenital disorders of sexual differentiation.Normal sexual differentiation
- male gonads.Embryology, anatomy and physiology
- diagnosis and treatment of climacteric neurosis
- menstrual cycle
- The use of estrogen for the treatment of climacteric neurosis
- The use of androgens in the treatment of climacteric neurosis
- Early puberty
- Menopause (Menopause) in men
- Principles of hormonal treatment of menstrual cycle disorders
- Principles of hormonal treatment of dysfunctional uterine bleeding
- Prevention of recurrence of dysfunctional uterine bleeding
- Climacteric neurosis in men
- Tumors Leydigovyh cells hilyusa ovarian
treatment Shereshevskii syndrome -Turner
in cases of growth less than 145 cm with open epiphyseal crevices can try to accelerate growth with the help of anabolic steroids, best methandrostenolone (dianabol), or Durabolin® (nandrolone), 15 mg per week.Note, however, that the anabolic steroids accelerate growth far in all patients, and only to a small extent.Treatment of patients is shown in which the first year of application of anabolic steroids has shown its effectiveness.In other cases, the patient shows the use of estrogen, causing feminization.Such treatment is, of course, is only symptomatic, but has on patients is very beneficial effect, improving their mental state, facilitating the sexual life, and so on. D. Usually applied estrogens in doses of 10 000 IU daily or every other day for 2-3 months continuously for the development ofgenital and then transferred to the introduction of said dose of estrogen in cycles of 20 days.A few days after cessation of estrogen occurs in patients with uterine krovootdelenie, and 5 days after the start of administration of estrogen begin again.It is also possible to carry out the introduction of the cyclical estrogen and progestins.The use of gonadotropins patients with gonadal dysgenesis is not shown because of their inefficiency.
If you suspect a tumor gonad development laparotomy with the audit of the pelvis.In cases where a tumor is detected, it must be removed.Furthermore, when the operation should be as prevention of tumor growth and remove rudiments gonads.If the tumor has proceeded with hyperandrogenism, patients shows amputation of the clitoris and cosmetic hair removal measures.In the next few days after the operation you can already begin to estrogen treatment.